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International Journal for Parasitology 38 (2008) 1257–1278
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Invited Review
Toxoplasma gondii infection in humans and animals in the United States
J.P. Dubey a,*, J.L. Jones b
a
United States Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Animal Parasitic Diseases
Laboratory, Building 1001, Beltsville, MD 20705-2350, USA
b
Division of Parasitic Diseases, National Center for Zoonotic, Vectorborne and Enteric Diseases, Coordinating Center for Infectious Diseases,
Centers for Disease Control and Prevention, 4770 Buford Highway, MS: F22, Chamblee, GA 30341, USA
Received 14 January 2008; received in revised form 11 March 2008; accepted 11 March 2008
Abstract
This paper reviews clinical and asymptomatic Toxoplasma gondii infection in humans and other animals in the USA. Seroprevalence
of T. gondii in humans and pigs is declining. Modes of transmission, epidemiology and environmental contamination with oocysts on
land and sea are discussed.
Published by Elsevier Ltd on behalf of Australian Society for Parasitology Inc.
Keywords: Toxoplasma gondii; Humans; Animals; Oocysts; Tissue cysts; USA
1. Introduction
Toxoplasma gondii infections are prevalent in humans
and animals worldwide (Dubey and Beattie, 1988). Felids
are the key animal species in the life cycle of this parasite
because they are the hosts that can excrete the environmentally-resistant stage, the oocyst. Humans become infected
post-natally by ingesting tissue cysts from undercooked
meat, consuming food or drink contaminated with oocysts,
or by accidentally ingesting oocysts from the environment.
However, only a small percentage of exposed adult humans
or other animals develop clinical signs of disease. It is
unknown whether the severity of toxoplasmosis in immunocompetent hosts is due to the parasite strain, host variability or other factors. Recently, attention has been
focused on genetic variability among T. gondii isolates
from apparently healthy and sick hosts.
It has been 100 years since the discovery and naming of
T. gondii. The parasite was ﬁrst found in laboratory animals (for history see Dubey, 2007). Its medical importance
remained unknown until 1939 when T. gondii was identiﬁed
*
Corresponding author. Tel.: +1 301 504 8128; fax: +1 301 504 9222.
E-mail address: [email protected] (J.P. Dubey).
conclusively in tissues of a congenitally-infected infant in
New York City, USA (Wolf et al., 1939), and its veterinary
importance became known when it was found to cause
abortion storms in sheep in 1957 in Australia (Hartley
and Marshall, 1957). In the present paper, we summarize
information on clinical and sub-clinical T. gondii infections
in humans and animals in the USA, including transmission,
epidemiology and control.
2. Clinical and asymptomatic Toxoplasma gondii infection in
humans and animals
2.1. Infection in humans
2.1.1. Asymptomatic infection
Infection with T. gondii can occur pre- or post-natally.
After birth, humans are usually infected with T. gondii by
ingestion of oocysts in soil or water that have been contaminated with cat feces, or by ingestion of tissue cysts in
undercooked meat (Dubey and Beattie, 1988; Bowie
et al., 1997; Bahia-Oliveira et al., 2003; Dubey, 2004; Jones
et al., 2005; de Moura et al., 2006). Transfusion or organ
transplantation from an infected person can also transmit
the organism (Shulman and Appleman, 1991; Schaﬀner,
0020-7519/$34.00 Published by Elsevier Ltd on behalf of Australian Society for Parasitology Inc.
doi:10.1016/j.ijpara.2008.03.007
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J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
2001). Most persons infected after birth are asymptomatic
(Montoya and Liesenfeld, 2004; Remington et al., 2006),
however, some develop a mild disease or in rare cases, a
more severe systemic illness (see Section 2.1.2). Once
infected, humans are believed to remain infected for life.
Unless immunosuppression occurs and the organism reactivates, people usually remain asymptomatic. However,
there is ongoing research on whether chronic T. gondii
infection has an eﬀect on reaction time (Havlı´cˇek et al.,
2001), tendency for accidents (Flegr et al., 2002), behavior
(Flegr et al., 1996, 2000; Laﬀerty, 2005, 2006) and mental
illness (Yolken et al., 2001; Flegr et al., 2003; Brachmann
et al., 2005; Brown et al., 2005).
Selected serological surveys in humans in the USA are
summarized in Table 1. Previous serological surveys were
summarized by Dubey and Beattie (1988). A recent serosurvey using samples from the population-based National
Health and Examination Nutrition Study (NHANES)
found a decrease in the age-adjusted T. gondii prevalence
in USA-born persons 12–49 years old from 14.1% in
1988–1994 to 9% in 1999–2004, a seroprevalence of 11%
in USA-born women 15–44 years old in 1999–2004, and
a seroprevalence of 28.1% in foreign-born women 1999–
2004 (Jones et al., 2007). The overall seroprevalence
(USA and foreign-born combined) increased with age
and was higher among non-Hispanic black persons and
Mexican Americans than among non-Hispanic white persons; however, among USA-born persons Mexican Americans had a lower seroprevalence than non-Hispanic
white or black persons (age 12–49, 5.1% versus 8.8% and
11.5%, respectively). An earlier study evaluating NHANES
III (1988–1994) sera for all persons 612 years of age (USA
and foreign-born combined) showed an overall ageadjusted seroprevalence of 22.5%, a relatively linear
increase in T. gondii infection with age, and a higher ageadjusted seroprevalence in the northeastern USA (29.2%)
compared with the South (22.8%), Midwest (20.5%) or
West (17.5%) (Jones et al., 2001). In this study, the risk
for T. gondii infection was higher among persons who were
foreign-born, had a lower education level, lived in crowded
conditions and worked in soil-related occupations. In a
separate study using NHANES III sera, the rate of T. gondii seropositivity among persons seropositive for the soil-
transmitted helminth Toxocara spp. was nearly double
the rate of T. gondii seropositivity among persons who were
not seropositive for Toxocara spp., suggesting that suﬃcient soil exposure to lead to Toxocara spp. infection doubles the risk of T. gondii infection (Jones et al., 2008).
Prior studies have also shown a decrease in T. gondii
seroprevalence in the USA over time. For example, in
1962 and 1989 T. gondii seroprevalence was examined
among military recruits, showing rates of 14.4% and
9.5%, respectively (Feldman, 1965; Smith et al., 1996).
Although not a complete sampling of the USA regional
populations, the studies in military recruits (Feldman,
1965; Smith et al., 1996) and an earlier study (Feldman
and Miller, 1956) found lower rates of T. gondii infection
in the West. The western region of the USA is generally
drier and oocysts may not survive as well in the soil in this
climate. However, due to variations in weather, cat populations and human behavior, there is likely to be a wide variation in T. gondii prevalence within regions of the USA.
2.1.2. Symptomatic infection
A minority of healthy persons infected with T. gondii
after birth develop symptoms, which are usually mild and
include manifestations such as fever, malaise and lymphadenopathy (Montoya and Liesenfeld, 2004; Remington
et al., 2006). However, in rare cases, humans who were previously healthy have developed severe and even fatal disease, including pulmonary and multivisceral involvement,
possibly from more virulent types of the organism (Carme
et al., 2002; Demar et al., 2007). In addition, up to 2% of
healthy persons in the USA infected with T. gondii develop
ocular disease (Holland, 2003), usually retinochoroiditis. A
higher percentage of infected persons have been documented to develop ocular disease in other parts of the
world, for example, one region of Southern Brazil (17.7%
with ocular lesions) (Glasner et al., 1992). Retinochoroiditis can be due to congenital or post-natally acquired disease and can be associated with acute infection or
reactivation (Montoya and Remington, 1996; Holland,
1999). Current thinking is that the majority of ocular toxoplasmosis comes from post-natally acquired disease (Holland, 1999, 2003). Acute toxoplasmic retinochoroiditis
results in pain, photophobia, tearing and loss of vision.
Table 1
Selected USA human Toxoplasma gondii antibody prevalence studies
Year sampled
Age group
Source of sera
No. tested
% Positive
Reference
1962
1987
1989
1992–1993
1988–1994
1999–2000
U.S. young adult
P18 years old
U.S. young adult
P18 years old
U.S. age-adjusted P12 years old
U.S. age-adjusted 12–49 years Women 12–49
years
U.S. age-adjusted 12–49 years Women 15–44
years
Military recruits
Maryland community
Military recruits
Illinois swine farm workers
NHANESa
NHANES
2680
251
2862
174
17,658
4234
14
31
9.5
31
22.5
15.8 14.9
Feldman (1965)
Roghmann et al. (1999)
Smith et al. (1996)
Weigel et al. (1999)
Jones et al. (2001)
Jones et al. (2003)
NHANES
15,960
10.8 11.0
Jones et al. (2007)
1999–2004
a
NHANES, National Health and Nutrition Examination Study.
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
Lesions tend to recur with progressive loss of vision over
time, especially when the lesions are near the central structures of the eye (Holland, 2003). Considering the prevalence of T. gondii infection and the estimate that up to
2% of persons with T. gondii infection have ocular lesions
in the USA (Holland, 2003), as many as 1.26 million persons in the USA may have ocular toxoplasmosis (based
on the 2000 census, Holland, 2003). A national survey of
ophthalmologists resulted in estimates that there were over
250,000 visits to ophthalmologists for active or inactive
ocular toxoplasmosis in a 2-year period, a relatively large
burden on the medical system (Lum et al., 2005).
2.1.2.1. Congenitally-infected children. Congenital toxoplasmosis generally occurs when a woman is newly infected
with T. gondii during pregnancy (Remington et al., 2006),
although rare exceptions have been reported in which
women were infected just before pregnancy (Vogel et al.,
1996). In addition, in immunosuppressed women reactivation of an infection acquired before pregnancy can lead to
congenital toxoplasmosis (Mitchell et al., 1990; Minkoﬀ
et al., 1997). The risk of congenital infection is lowest when
maternal infection is in the ﬁrst trimester (10–15%) and
highest when infection occurs during the third trimester
(60–90%) (Dunn et al., 1999; Foulon et al., 1999; Remington et al., 2006). However, congenital infection usually
leads to more severe disease when it occurs in the ﬁrst trimester (Desmonts and Couvreur, 1974; Holliman, 1995;
Remington et al., 2006). Congenital infection can lead to
a wide variety of manifestations in the fetus and infant
including spontaneous abortion, still-birth, a live infant
with classic signs of congenital toxoplasmosis such as
hydrocephalus or microcephalus, cerebral calciﬁcations
and retinochorioditis, an infant who fails to thrive or has
CNS involvement or retinochoroiditis, or an apparently
normal infant who develops retinochoroiditis or symptoms
of CNS involvement later in life (McAuley et al., 1994;
Remington et al., 2006). Most children are asymptomatic
at birth (Guerina et al., 1994), but many will develop ocular
or neurological manifestations (including learning disabilities) later in life (Wilson et al., 1980; Koppe et al., 1986;
Guerina et al., 1994; Dunn et al., 1999; McLeod et al.,
2006; Systemic Review on Congenital Toxoplasmosis
Study Group, 2007).
In the USA, the most complete data on the rate of congenital infection comes from the New England Regional
Newborn Screening Program, which serves Massachusetts
and New Hampshire. All infants born in the catchment
area are screened for a variety of conditions including T.
gondii infection. Of the 635,000 infants who underwent
serological testing between 1986 and 1992, 52 were
infected, resulting in an infection rate of approximately 1
per 10,000 births. Only two (4%) of these infants were recognized to have congenital toxoplasmosis before the
screening results were known; however, follow-up examinations identiﬁed signs of disease in 40% of the infants (Guerina et al., 1994). A subsequent study on the epidemiology
1259
of congenital toxoplasmosis identiﬁed in the New England
Regional Newborn Screening Program 1988–1999 reported
a rate of approximately 1 per 12,000 live births (Jara et al.,
2001). Older prospective studies in Alabama and New
York reported in the 1970s found rates of congenital toxoplasmosis of 13 per 10,000 and seven per 10,000 births,
respectively (Kimball et al., 1971; Alford et al., 1974).
2.1.2.2. Immunosuppression. Toxoplasmic encephalitis is
the most common clinical presentation of toxoplasmosis
among persons with AIDS. It is usually the result of reactivation of latent tissue cysts (Luft et al., 1983, 1984; Wong
et al., 1984; Israelski et al., 1993) when persons become
severely immunosuppressed, with the highest risk occurring
when the CD4+ T-lymphocyte count drops below 50 cells
per microliter (Luft et al., 1983, 1984; Wong et al., 1984;
Porter and Sande, 1992; Jones et al., 1996; Leport et al.,
1996). The clinical presentation often includes a focal
encephalitis with headache, confusion, motor weakness
and fever and, if not treated, can progress to seizures, stupor and coma (Luft et al., 1983, 1984; Wong et al., 1984).
Speech abnormalities and hemiparesis are the most common focal neurological ﬁndings (Luft et al., 1993). The primary lesion is cerebral necrosis, particularly of the
thalamus (Renold et al., 1992). Pneumonia, other disseminated systemic disease or retinochoroiditis can be seen but
are not as common as toxoplasmic encephalitis in HIVinfected persons. Clinically severe toxoplasmosis can also
occur in immunosuppressed persons with malignancies
and after transfusions (rarely) or transplants with immunosuppressive therapy (Siegel et al., 1971; Shulman and
Appleman, 1991; Schaﬀner, 2001).
In the era before highly active antiretroviral therapy
(prior to the mid-1990s), the annual incidence of toxoplasmic encephalitis was up to 33% among T. gondii seropositive
HIV-infected
persons
with
advanced
immunosuppression who were not receiving prophylaxis
with drugs active against T. gondii (Benson et al., 2004.
Treating opportunistic infections among HIV-infected
adults and adolescents. AidsInfo, U.S. Department of
Health and Human Services, accessed 1/10/08 http://aidsinfo.nih.gov/contentﬁles/TreatmentofOI_AA.pdf, pp. 9–
12). In another study, the annual incidence was 38% among
T. gondii seropositive persons with AIDS who were studied
over 2 years (Israelski et al., 1993). An analysis of 90 inpatient and outpatient facilities in nine USA cities from January 1990 through August 1995 found an incidence rate of
toxoplasmic encephalitis of 4.0 cases per 100 person-years
among HIV-infected persons with a CD4+ T-lymphocyte
count less than 100 cells per microlitre (Jones et al.,
1996). However, during the years that prophylaxis and
highly active antiretroviral therapy became widely used
(mid-1990s in most developed countries), the incidence
and deaths associated with toxoplasmic encephalitis
declined markedly (Jones et al., 1999, 2002; Kaplan et al.,
2000; Hooshyar et al., 2007). A French study found that
the rate of toxoplasmic encephalitis declined from 3.9 cases
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J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
per 100 person-years in the time before the availability of
highly active antiretroviral therapy (1992–1995) to 1 case
per 100 person-years after it was available (1996–1998)
(Abgrall et al., 2001). A decline to a similar incidence level
was shown during the same time period across 11 USA cities (Kaplan et al., 2000).
2.2. Toxoplasma gondii infections in other animals
2.2.1. Livestock
Poultry, pigs and cattle are the main species of livestock
in USA. Clinical toxoplasmosis is not a major problem in
these animals.
2.2.1.1. Pigs. Seroprevalence data are summarized in Table
2. Prevalence of T. gondii varies dramatically among the
classes of pigs surveyed (market pigs versus sows, indoor
pigs with a biosecurity system versus free-range). The pigs
used for unprocessed pork consumption (feeder pigs, market pigs) are mostly raised indoors in well managed facilities to prevent access to rodents and cats. In these well
managed facilities, prevalence of T. gondii has greatly
declined in the last decade (Table 2). In a statistically valid
population-based nationwide survey conducted in 1983–
1984, seroprevalence was 23% in market pigs and 42% in
breeder pigs (sows) (Dubey et al., 1991). When pigs from
these same areas were tested in 1992, prevalence had
dropped to 20.8% in breeders and 3.1% in ﬁnisher pigs
(Dubey et al., 1995c). The institution of a National Animal
Health Monitoring System (NAHMS) for swine now
allows periodic surveillance of pigs for microbial infections.
The prevalence of T. gondii in three NAHMS swine surveys
in 1990, 1996 and 1998 showed a steady decline (Table 2).
The prevalence of T. gondii in pigs is also inﬂuenced by
management systems. In poorly managed non-conﬁnement
systems, prevalence runs as high as 68% (Table 2). Risk
assessment studies indicated that exposure to cats (oocysts)
and mice, and not outdoor housing, were associated with
T. gondii infection in pigs (Weigel et al., 1995b).
Viable T. gondii was isolated from 0.3% to 92.7% of pigs
surveyed, depending on the source of pigs, class of pigs and
the type of pork tested (Table 3). Seropositivity in general
is a good indicator of the presence of viable parasites. In
one study of 1000 sows, 22% were seropositive and viable
T. gondii was isolated from 17% of these using heart tissue
for bioassays; the isolation rate would likely have been
higher if additional tissues were sampled. In another study,
viable T. gondii was isolated from 51 of 55 pigs when hearts
and tongues were used for testing (Table 3).
As mentioned earlier, clinical toxoplasmosis in pigs is
rare. Toxoplasmosis was ﬁrst reported in pigs on a farm
in Ohio, USA (Farrell et al., 1952; Sanger and Cole,
1955). Pigs on this farm were reported to have cough, lack
of coordination, tremors and diarrhea, with a 50% mortality rate. There were still-births, premature births and
deaths soon after birth. Viable T. gondii were found in colostrums and sows’ milk. These ﬁndings have not been conﬁrmed and it seems likely that the outbreak was
complicated by other causes (Dubey and Beattie, 1988).
Dubey et al. (1979) described acute toxoplasmosis in a pig-
Table 2
Prevalence of Toxoplasma gondii antibodiesa in sera of pigs from the USA
Year sampled
1983–1984
1989–1992
1989–1990
1990
1991–1992
1992
1992–1993
1994–1995
1994–1995
1998
2000
2002
2006
a
b
c
d
e
Type
Source of sera
Market hogs
Sows
Sows
All ages
Sows
Sows
Nationwide
Market hogs
Sows
Market hogs
Sows
Market hogs
Market hogs
Sows
Various ages
Illinois-179 herds
Market hogs
Sows
Market hogs
Market hogs
Abattoir-Iowa
31 Farms-Hawaii
NAHMSb
Tennessee-343 herds
Illinois-47 herds
North Carolina-14 herds
NAHMS
Connecticut, Massachusetts, NewHampshire, Rode Island,
Vermont
NAHMS
Massachusetts-1 herd
Maryland-1 herd
Modiﬁed agglutination test, 1:20 or higher dilution.
National Animal Health Monitoring System.
Declining seroprevalence in market pigs.
Patton et al. (1998).
Patton et al. (2000).
No. tested
11,229
623
1000
509
3479
3841
% Positive
c
23
42
22.2
48.5
20
36
1885
5080
4252
2617
2238
4712
3236
1897
3.1c
20.8
2.3c
15.1
0.5c
3.2c
15
47.5
8086
5720
55
48
0.9c
6
87.2
68.7
Reference
Dubey et al. (1991)
Dubey et al. (1995a)
Dubey et al. (1992c)
Patton et al. (1996)
Assadi-Rad et al.
(1995)
Weigel et al. (1995a)
Dubey et al. (1995c)
Davies et al. (1999)
d
Gamble et al. (1999)
e
Dubey et al. (2002a)
Dubey et al. (2008b)
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
1261
Table 3
Isolation of Toxoplasma gondii from various food animals in the USA
Species
Source
No. bioassayed and tissue
% Positive
Reference
Pigs
Abattoir-Maryland
Abattoir, Iowa
Massachusetts-1 herd
Retail meat, nationwide
Maryland-1 herd
Abattoir-Maryland
Retail meat
Abattoir-Maryland
Abattoir-Maryland
Abattoir-Ohio
Retail meat, nationwide
Retail meat, nationwide
Alabama
Mississppi
Iowa, Minnesotta
Pennsylvania
Pennsylvania
50 diaphragms
1000 sow hearts
55 market hogs Hearts and tongues
2094 pork
36 hearts
86
50 lamb chops
68 lamb hearts
60 diaphragms
350 mixed tissues
2094 beef
2094 breast meat
19
73
88
28
10
24
17
92.7
0.3
36.8
9.2
4
77.9
0
0
0
0
21
28.7
17
35.7
70
Jacobs et al. (1960)
Dubey et al. (1995a)
Dubey et al. (2002a)
Dubey et al. (2005b)
Dubey et al. (2008b)
Jacobs et al. (1960)
Remington (1968)
Dubey et al. (2008c)
Jacobs et al. (1960)
Dubey and Streitel (1976)
Dubey et al. (2005b)
Dubey et al. (2005b)
Lindsay et al. (1991)
Dubey et al. (2004b)
Dubey et al. (2008)
Dubey et al. (1995b)
Dubey et al. (2004b)
Sheep
Cattle
Chickens
Deer
Black bear
let on a farm in Indiana, USA. This piglet had necrosis of
intestine, lymphadenitis, pneumonia and encephalitis; tachyzoites were demonstrable in lesions. This piglet and 15 littermates were apparently normal at birth, but developed
diarrhea within 1–2 weeks, and eight of those died within
3–4 weeks. Epidemiological data indicated that the piglets
probably became infected with T. gondii oocysts after birth
(Dubey et al., 1979). Although congenital toxoplasmosis
can be induced in pigs (Dubey et al., 1990a), we are not
aware of a documented case of toxoplasmic abortion in
pigs in the USA or elsewhere.
2.2.1.2. Cattle. Cattle are considered a poor host for T.
gondii. Although cattle can be successfully infected with
T. gondii oocysts, the parasite is eliminated or reduced to
undetectable levels within a few weeks (Dubey, 1983,
1986), perhaps due to innate resistance. In one experiment,
four steers weighing 100–150 kg were each fed 10,000
oocysts and killed 350, 539, 1191 and 1201 days p.i. (Dubey
and Thulliez, 1993). At necropsy, many tissues from each
animal were bioassayed (100 g each for bioassay in mice
and 500 g each for bioassay in cats) for viable T. gondi.
Viable T. gondii were isolated from steers killed 350 to
1191 days p.i. by bioassays in cats but not by bioassays
in mice. The fourth steer became seronegative 15 months
p.i. and viable T. gondii was not isolated from any tissue
either in cats or mice. In another study, an attempt was
made to isolate T. gondii from a naturally-exposed beef
cow (Dubey, 1992). This 500 kg cow was killed and 100–
500 g portions of its tissues were bioassayed in cats (500 g
of each tissue) and mice (100 g of each tissue). None of
the 12 cats fed approximately 6 kg of beef shed oocysts.
Viable T. gondii was not isolated from any of the edible tissues of the cow by bioassays in mice but was isolated from
a homogenate of intestine of the cow. Results of these
experiments highlight the diﬃculties in detecting T. gondii
infection in cattle. Other attempts to isolate T. gondii from
beef are given in Table 3.
Little is known about the speciﬁcity and sensitivity of
serological diagnosis of T. gondii infection in cattle because
several tests that are used to diagnose toxoplasmosis in
humans give erratic results with cattle sera (Dubey et al.,
1985b), and it is diﬃcult to verify speciﬁcity using naturally-infected cattle. The dye test, which is the most speciﬁc
test for humans, gives false or erratic results with cattle sera
(Dubey et al., 1985b; Dubey and Thulliez, 1993). Among
all serological tests evaluated, a titer of 1:100 or higher in
the modiﬁed agglutination test (MAT) appears to be indicative of T. gondii infection in cattle. In one serological survey of T. gondii in cattle from Montana, 3.2% of 2539 cattle
had MAT titers of 1:128–1:512 (Dubey, 1985). In a study
of beef from retail grocers, antibodies to T. gondii were
not found by ELISA in meat juice from any of the 2049
samples of beef bioassayed during the National Retail
Meat Survey for T. gondii, nor were viable organisms
detected (Dubey et al., 2005b).
There are no conﬁrmed reports of clinical toxoplasmosis
in cattle (Dubey, 1986). Before the discovery of Neospora
caninum as a cause of abortion in cattle (Thilsted and
Dubey, 1989) it is likely that this parasite in cattle was misdiagnosed as T. gondii; T. gondii and N. caninum are morphologically similar parasites (Dubey et al., 1988c). Viable
T. gondii was isolated from an aborted fetus from a cow in
Washington State, USA (Canada et al., 2002). Whether the
cow had aborted due to toxoplasmosis could not be determined because a histological examination of the fetus was
not made. These authors reviewed other attempts to isolate
T. gondii from bovine fetuses in the USA (Canada et al.,
2002).
2.2.1.3. Poultry. In a recent survey, viable T. gondii was not
isolated from chicken breast meat samples obtained from
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J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
retail meat stores (Table 3), however, meat juice from 1.4%
of chickens had antibodies to T. gondii (Dubey et al.,
2005b). There is no other serological survey for T. gondii
in chickens raised in large-scale conﬁnement operations.
Jacobs and Melton (1966) isolated viable T. gondii from
ovaries and oviducts of three and leg muscle of one of
108 chickens from a slaughter house in Maryland; the
source of these chickens was not known.
Unlike chickens raised in conﬁnement, backyard raised
chickens are commonly infected with T. gondii. Viable T.
gondii was isolated from 27% to 100% of chickens from
backyard operations on small farms in Mississippi, Montana, Texas, Ohio, Illinois, Georgia and Louisiana (Gibson
and Eyles, 1957; Eyles et al., 1959; Foster et al., 1969;
Dubey, 1981, in press; Dubey et al., 2003a, 2007b); these
chickens were primarily kept for egg production.
There are three reports of clinical toxoplasmosis in
chickens from the USA. Ostendorf and Henderson
[Ostendorf and Henderson, 1962. Toxoplasmosis in chickens. Proc. XII World Poultry Congress, Sydney, Australia, Section paper 385, pp. 385–387] reported that
chickens with toxoplasmic encephalitis and chorioretinitis
died on chicken farms in Indiana. Goodwin et al. (1994)
reported peripheral neuritis in three chickens from Georgia and the diagnosis was made immunohistochemically,
however herpes virus infection (Marek’s disease) could
not be ruled out. More recently, in a group of 14 backyard chickens in Illinois, three birds died suddenly (Dubey
et al., 2007b). Torticollis, an inability to stand, and lateral
recumbancy were the only clinical signs. One of these
birds was necropsied. Marked lesions were limited to
the brain which had multiple areas of necrosis, perivascular lymphocytic cuﬀs and gliosis. An unusual ﬁnding was
the presence of numerous tissue cysts and tachyzoites in
lesions. The remaining 11 chickens remained asymptomatic and all contained viable T. gondii (Dubey et al.,
2007b).
2.2.1.4. Sheep. The prevalence of T. gondii in adult sheep
and lambs in the USA is high (Tables 3 and 4). Toxoplasma
gondii causes abortion and neonatal mortality in sheep
worldwide. Isolated occurrences and epidemics of abortion
and neonatal mortality have been reported in sheep in the
USA (Dubey et al., 1981a, 1986b, 1990b; Dubey and Kirkbride, 1989a, 1990; Dubey and Welcome, 1988). Congenitally-infected lambs that survive the ﬁrst week after birth
usually grow normally and can be a source of infection
for humans. An example is given here. Dubey and Kirkbride (1989b) isolated T. gondii from eight of eight naturally-infected lambs from a ﬂock in South Dakota, USA.
The lambs were from a ﬂock that had aborted due to toxoplasmosis. Toxoplasma gondii was found histologically in
11 of 30 lambs that were born dead. Lambs that survived
the ﬁrst week after birth remained asymptomatic and were
bled at 3–4 months of age; antibodies (MAT 1:1024 or
higher) were found in 67 of 112 lambs. Eight of these lambs
with MAT titers of 1:4096 or higher were slaughtered when
they were 7 months old. Toxoplasma gondii was isolated
from the hearts of three, tongues of seven, leg of lamb in
eight, and lamb chops of seven by bioassays of 100 g of
each tissue in mice (Dubey and Kirkbride, 1989b). There
is no documented case of clinical toxoplasmosis in adult
sheep in the USA or elsewhere. The case of encephalomyelitis in an adult sheep in New York, USA by Olafson and
Monlux (1942) is now considered to have been due to a
Sarcocystis-like parasite (Dubey and Beattie, 1988).
2.2.1.5. Goats. The number of goats in the USA is small
and they are often raised in small operations. Most of the
goats raised in the USA are dairy goats and females are
used to produce milk and cheese. Although abortion and
neonatal mortality are the main clinical signs, adult goats
can develop clinical toxoplasmosis involving liver, kidneys
and brain (Dubey and Beattie, 1988). Abortion and neonatal mortality was reported in dairy goats in Montana, Connecticut, and Maryland (Dubey, 1981; Dubey et al., 1981a,
1986a) in the USA.
2.2.1.6. Horses. Horses are resistant to T. gondii. Two
recent surveys indicate a low prevalence of T. gondii in
horses (Table 4). We are not aware of any conﬁrmed report
of clinical toxoplasmosis in horses anywhere in the world.
2.3. Pets and other animals
2.3.1. Domestic cats (Felis domesticus)
Toxoplasma gondii infection in cats is both of epidemiological and clinical signiﬁcance. There has been no nationwide survey of the prevalence of T. gondii in cats in the
USA and the available data were summarized by Conrad
et al. (2005). In the largest survey using convenience samples from sick cats submitted for diagnosis to a clinical laboratory, antibodies to T. gondii were found in 31% of
12,628 cats (Vollaire et al., 2005). The seroprevalence of
T. gondii varies with the age and lifestyle of the cat (Dubey,
1973).
The prevalence of T. gondii was higher in feral than pet
or owned cats (Table 5). These data are comparable among
diﬀerent categories of cats because results are based on 1:25
serum dilution tested by the MAT and most of those were
performed in one laboratory.
Cats can suﬀer from clinical toxoplasmosis (Meier et al.,
1957; Dubey and Carpenter, 1993a,b; Dubey and Lappin,
2006). Aﬀected cats may appear depressed and anorexic
and die suddenly with no obvious clinical signs. Pneumonia
is the most important clinical manifestation of feline toxoplasmosis. Other common clinical manifestations are hepatitis, pancreatic necrosis, myositis, myocarditis, uveitis,
dermatitis and encephalitis. Clinical toxoplasmosis is most
severe in congenitally infected kittens. Among 100 histologically conﬁrmed cases of toxoplasmosis in cats, 36 were
considered to have generalized toxoplasmosis, 36 pulmonary, 16 abdominal, two hepatic, one pancreatic, one cardiac, two cutaneous and seven neurologic; in 14 cats
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
1263
Table 4
Serological prevalence of Toxoplasma gondii in selected species of animals in the USA
Species
Locality and source
Year
Sheep
New Jersey, New York,
Pennsylvania
California, Idaho, New
England, Oregon
Idaho
Maryland
New York
Not stated
Adults-309a Lambs-345a
1974–1976
Ewes-2164a Lambs-1056a
Not stated
1984
1987
Ewes-250b
Sheep-78b
Ewes-592b
Goats
Horses
Wild pigs
White-tailed deer
Black bear (Ursus
americanus)
Raccoon (Procyon
lotor)
a
b
Number tested
% Positive
62.4:55.0
24:8
Serologic
test
ELISA
Cut-oﬀ
value
?
Reference
Malik et al. (1990)
IHAT
1:64
Riemann et al. (1977)
20.8
41
73.8
IHAT
MAT
MAT
1:64
1:16
1:16
Iowa, Minnesotta, South
Dakota, Kansas
Maryland, Virginia
California
1983–1987
Ewes-1564b
65.8
MAT
1:64
2006
1974–1977
Lambs-383a
Dairy goats-1054b
27.1
23
MAT
IHAT
1:25
1:64
Washington
1982–1984
Dairy goats-1000
22.1
MAT
1:40
Nationwide
1973
1294
20
IHAT
1:64
Midwest
1976–1977
500a
10
DT
24 states
Wyoming
California
Georgia (mainland)
(Ossawa island)
South Carolina
1998
2002
1982–1983
1979–1980
1992–1994
1990
1054a
276b
135
170
1,064
180
6.9
0.2
17
18.2
0.9
31
MAT
MAT
LAT
MAT
MAT
MAT
1:20
1:25
1:32
1:25
1:25
1:32
Pennsylvania
1991
583
60
MAT
1:25
Minnesotta
Mississippi
Iowa
Pennsylvania
Pennsylvania
Pennsylvania
Pennsylvania
1990–1993
2002–2003
2007
1989–1992
1993
1998
2007
1367
73
84
665
28
80
37
30
46.5
64.2
80
78.5
80.5
75.6
MAT
MAT
MAT
MAT
MAT
MAT
MAT
1:25
1:25
1:25
1:25
1:25
1:25
1:25
North Carolina
Iowa, New Jersey, Ohio,
South Carolina,
Pennsylvania
Kansas
Illinois
Iowa
Illinois
Florida, New Jersey,
Pennsylvania,
Massachusetts
Virginia
Wisconsin
1996–1997
Not stated
143
427
84
50.3
MAT
MAT
1:25
1:25
Huﬀman et al. (1981)
Dubey et al. (1986b)
Dubey and Welcome
(1988)
Dubey and
Kirkbride (1989a)
Dubey et al. (2008c)
Ruppanner et al.
(1978)
Dubey and Adams
(1990)
Riemann et al.
(1975c)
Al-Khalidi and
Dubey (1979)
Dubey et al. (1999)
Dubey et al. (2003c)
Clark et al. (1983)
Dubey et al. (1997a)
Dubey et al. (1997a)
Diderrich et al.
(1996)
Humphreys et al.
(1995)
Vanek et al. (1996)
Dubey et al. (2004b)
Dubey et al. (2008d)
Briscoe et al. (1993)
Dubey et al. (2004b)
Dubey et al. (2004b)
Dubey, J.P.,
unpublished data
Nutter et al. (1998)
Dubey et al. (1992b)
1989–1993
1992–1993
1984–1988
1989–1993
1993–1996
20
188
885
379
99
70
67
15
49
46
MAT
MAT
MAT
MAT
MAT
1:25
1:25
1:32
1:25
1:50
Brillhart et al. (1994)
Dubey et al. (1995c)
Hill et al. (1998)
Mitchell et al. (1999)
Lindsay et al. (2001)
2000–2001
2006
256
54
84.4
59.2
MAT
MAT
1:25
1:25
Hancock et al. (2005)
Dubey et al. (2007a)
1:2
Abattoir.
Farms.
concurrent microbial or other conditions were identiﬁed
(Dubey and Carpenter, 1993a).
Cats, like humans, suﬀer from an immunodeﬁciency
virus (FIV). Although FIV infection can experimentally
predispose cats to generalized toxoplasmosis (Davidson
et al., 1993), this phenomenon appears to be rare in natu-
rally-infected cats as there are only a few reports of fulminating toxoplasmosis in cats with FIV (Heidel et al., 1990;
Dubey and Lappin, 2006). The interaction between T. gondii and FIV is intriguing because both the seroprevalence
and the magnitude of titers were higher in dually infected
cats (Witt et al., 1989).
1264
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
Table 5
Seroprevalence of Toxoplasma gondii in domestic cats (Felis domesticus) from the USA according to the type and habitat of the cat
Cat type
Locality
No. tested
% Positive
Reference
Goat farm
Sheep farm
Pig farms
Pig farms
Feral
Rural
Barn
Outside
Feral
Marland
Maryland
Iowa
Illinois
Iowa
Ohio
4
16
74
391
20
100
100b
41.9
68.3
80
Dubey et al. (1986a)
Dubey et al. (1986b)
Smith et al. (1992)
Dubey et al. (1995c)
Hill et al. (1998)
Dubey et al. (2002b)
94
80
78
50
38
62
84
116
50
36
100
76
63
34
Rhode Island
Shelter
Owned
DeFeo et al. (2002)
North Carolina
Feral
Owned
a
b
Nutter et al. (2004)
Data based on modiﬁed agglutination test.
Viable T. gondii isolated from tissues of nine of 16 cats.
2.3.2. Dogs
Primary toxoplasmosis in dogs is rare. Most cases of
acute toxoplasmosis in the USA were observed in dogs
not vaccinated against the immunosuppressive canine distemper virus (CDV) (Capen and Cole, 1966; Dubey and
Beattie, 1988; Dubey et al., 1989; Rhyan and Dubey,
1992). The most severe disease occurs in pups but to our
knowledge there is no documented case of congenital toxoplasmosis in dogs. Common clinical manifestations of
toxoplasmosis in dogs are pneumonia, hepatitis and
encephalitis (Dubey and Lappin, 2006).
2.3.3. Other pets
Sporadic cases of clinical toxoplasmosis occur in rabbits
(Leland et al., 1992; Dubey et al., 1992a), squirrels (van
Pelt and Dieterich, 1972; Soave and Lennette, 1959; Dubey
et al., 2006; Bangari et al., 2007), mink (Frank, 2001) and
pet birds, especially in canaries and ﬁnches (Dubey, 2002;
Dubey et al., 2004a). Toxoplasmosis in squirrels can simulate signs of rabies (Soave and Lennette, 1959). Reported
clinical signs in squirrels were anorexia, diarrhea, lethargy,
viciousness, labored breathing and in two cases squirrels
had bitten children. An unusual clinical presentation of
toxoplasmosis in canaries is blindness with almost complete destruction of the eyes (Dubey, 2002).
2.4. Wild animal species, including game
Among wild animals, T. gondii infections in deer, bears
and raccoons are of epidemiological signiﬁcance and prevalence data are summarized in Table 4. Deer are strictly
herbivores and the high prevalence of T. gondii in deer suggests widespread contamination of the environment with
oocysts. Bears and raccoons are omnivores and infections
in those indicate cumulative contamination with oocysts
and intermediate hosts in the environment. In one survey,
antibodies to T. gondii were found in 85.9% of red foxes
(Vulpes vulpes) and gray foxes (Urocyon cinereoargenteus)
in Kentucky, Indiana, Michigan and Ohio, and viable T.
gondii was isolated from both of these hosts (Walton and
Walls, 1964; Dubey et al., 2004b).
2.5. Captive zoo animals and endangered species
Certain species of zoo animals, especially New World
primates, wallabies and kangaroos, are highly susceptible
to toxoplasmosis (Ratcliﬀe and Worth, 1951; Dubey and
Beattie, 1988). Acute toxoplasmosis has been described in
ring-tailed lemurs, Lemur catta (Dubey et al., 1985a; Spencer et al., 2004), squirrel monkeys, Saimiri sciureus (McKissick et al., 1968; Anderson and McClure, 1982), marmoset,
Oedipomidus oedipus (Benirschke and Richart, 1960), and
wooley monkey, Lagothrix sp. (Hessler et al., 1971). These
animals can die suddenly, often with visceral toxoplasmosis, before the lesions develop in the brain. Enteritis characterized by necrosis of the cells of lamina propria and
mesenteric lymphadenitis suggest oral infection with food
and water contaminated with oocysts. Old World primates
are generally resistant to clinical toxoplasmosis but there is
a report of toxoplasmosis in macaques, Macacca mulata
(Wong and Kozek, 1974).
There are many reports of severe toxoplasmosis in wallabies and kangaroos in zoos worldwide, including from
the USA (Boorman et al., 1977; Dubey et al., 1988b; Miller
et al., 1992; Adkesson et al., 2007). Among marsupials,
macropodids are highly susceptible to acute toxoplasmosis.
Clinical signs include pneumonia, myocarditis, hepatitis
and blindness, and they can die even after treatment with
sulfonamides and pyrimethamine (Dubey and Crutchley,
2008).
Toxoplasmosis in the endangered Hawaiian crow (Corvus hawaiiansis) is of particular interest because there are
few (<25) animals left and four animals in the wild died
of clinical toxoplasmosis (Work et al., 2000).
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
2.6. Marine mammals
Recent ﬁndings of T. gondii infection in marine mammals in the USA are most intriguing. In a preliminary
report Thomas and Cole (1996) reported protozoal encephalitis in 8.5% of sea otters. Before this, there were isolated
reports of T. gondii-associated encephalitis in other marine
mammals including seals, sea lions and dolphins, and these
were summarized by Dubey et al. (2003b). The sea otter is
listed as an endangered species (Conrad et al., 2005). Two
groups of researchers made detailed studies of causes of
mortality in sea otters. Of the 105 otters necropsied at
the Californian laboratories from 1998 to 2001, T. gondii
was considered to be the primary cause of death in 17
and a related parasite, Sarcocystis neurona in seven otters
(Kreuder et al., 2003). Otters with preexisting T. gondii
encephalitis were considered prone to shark attack (Kreuder et al., 2003). In another investigation involving otters
that died in California and Washington State but necropsied at the National Wildlife Health Center in Wisconsin,
protozoal encephalitis was considered the cause of death
in 39 of 334 (11.3%) sea otters; of these 22 were infected
with S. neurona, ﬁve with T. gondii and 12 had dual infections (Thomas et al., 2007). Thus, T. gondii was not a major
cause of mortality in these sea otters.
Antibodies to T. gondii were found in a variety of marine mammals including sea otters, dolphins, seals and walruses (Table 6). Prevalence of T. gondii in sea otters was
high but varied between 47% and 100%, depending on
the category (live versus dead), source (California versus
Washington), and the serological test used. Prevalence in
sea otters from California was higher than in Washington
otters. Although T. gondii were not found in 65 sea otters
from Alaska (Miller et al., 2002a), antibodies were found
in other marine mammals from Alaska (Table 6). Both
antibodies and clinical toxoplasmosis were found in the
1265
Hawaiian monk seal (Monachus schauinslandi), indicating
water in the Paciﬁc Ocean is infected (Honnold et al.,
2005; Aguirre et al., 2007).
The high seroprevalence of T. gondii antibodies in sea
otters has been veriﬁed parasitologically. Viable T. gondii
was isolated from 85 sea otters from California and Washington (Cole et al., 2000; Miller et al., 2002b; Conrad et al.,
2005; Sundar et al., 2008).
A very high seroprevalence of T. gondii was found in the
bottlenose dolphin (Tursiops truncatus) from California,
Florida, North Carolina and South Carolina, indicating
that marine mammals on both coasts of the USA are
exposed to T. gondii (Table 6). Recently, viable T. gondii
was isolated from bottlenose dolphins (Dubey et al., in
press c). Transplacental toxoplasmosis is considered rare
in marine mammals (Dubey et al., 2003b; Miller et al.,
2008).
2.7. Pathogenesis of toxoplasmosis including T. gondii
genotype
Only a small percentage of exposed adult humans or
animals develop clinical toxoplasmosis. It is unknown
whether the severity of toxoplasmosis in immunocompetent individuals is due to the parasite strain, host variability
or other factors. Experimentally, oocyst-induced infections
are more severe than those induced by tissue cysts and
bradyzoites by the natural oral route, irrespective of the
dose (Dubey and Frenkel, 1973; Dubey and Beattie,
1988; Dubey, 1997; Dubey et al., 1997b). Severe clinical
toxoplasmosis was reported in humans and was linked epidemiologically to ingestion of T. gondii oocysts in food or
water (Teutsch et al., 1979; Benenson et al., 1982; Bowie
et al., 1997; de Moura et al., 2006). Little is known about
the eﬀect of race or geography on clinical toxoplasmosis
in humans, except that there is a high prevalence of eye dis-
Table 6
Prevalence of Toxoplasma gondii antibodies in marine mammals in the USA
Species
Source
No. tested
% Positive
Test
Titer
Reference
Sea otters (Enhydra lutris)
California – live
Dead
Live
Dead
Washington live
Dead
Alaska
Alaska
California
Washington
Alaska
Alaska
Alaska
Alaska
Hawaii
California
Florida
Florida, South Carolina
South Carolina
80
77
100
25
21
10
53
27
18
380
311
32
8
9
117
94
47
146
49
36
61
82
52
38
100
5.6
29.6
61.1
7.6
16.4
15.6
50
11.1
1.7
96.8
100
100
53
IFAT
IFAT
MAT
MAT
IFAT
MAT
MAT
MAT
MAT
MAT
MAT
MAT
MAT
MAT
MAT
MAT
MAT
MAT
MAT
1:320
Miller et al. (2002a)
Miller et al. (2002a)
Dubey et al. (2003b)
Sundar et al. (2008)
Miller et al. (2002a)
Sundar et al. (2008)
Dubey et al. (2003b)
Dubey et al. (2003b)
Dubey et al. (2003b)
Lambourn et al. (2001)
Dubey et al. (2003b)
Dubey et al. (2003b)
Dubey et al. (2003b)
Dubey et al. (2003b)
Aguirre et al. (2007)
Dubey et al. (2003b)
Dubey et al. (2003)
Dubey et al. (2005a)
Dubey et al. (2008e)
Walruses (Obobenus rosmarus)
Sea lions (Zalophus californianus)
Harbor seals (Phoca vitulina)
Ringed seal (Phoca hispida)
Bearded seals (Erignathus barbatus)
Spotted seals (Phoca largha)
Hawaiian monk seal (Monachus schauislandi)
Bottlenosed dolphin (Tursiops truncatus)
1:25
1:25
1:320
1:25
1:25
1:25
1:25
1:25
1:25
1:25
1:25
1:25
1:25
1:25
1:25
1:25
1:25
1266
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
ease in southern Brazil (Glasner et al., 1992; Silveira et al.,
2001; Holland, 2003).
Recently, attention has been focused on genetic variability among T. gondii isolates from apparently healthy and
sick hosts. Toxoplasma gondii isolates have been classiﬁed
into three genetic Types (I, II, III) based on restriction fragment length polymorphism (RFLP) (Howe and Sibley,
1995) and until recently, T. gondii was considered to be clonal with very little genetic variability. Based on newer markers for genetic characterization and using recently isolated
strains, a higher genetic variability has been revealed than
was previously reported (Ajzenberg et al., 2002; Ajzenberg
et al., 2004; Khan et al., 2006; Lehmann et al., 2006).
Circumstantial evidence suggests that certain genetic
types of T. gondii may be associated with clinical toxoplasmosis in humans in the USA (Howe et al., 1997; Grigg et al.,
2001; Boothroyd and Grigg, 2002; Khan et al., 2005, 2006).
It has been suggested that Type I isolates or recombinants
of Types I and III are more likely to result in clinical toxoplasmosis (see Khan et al., 2005, 2006 and references contained therein), but genetic characterization has essentially
been limited to isolates from patients with toxoplasmosis.
In France, of the 86 T. gondii isolates obtained from
patients with clinical toxoplasmosis, 73 (84.8%) were Type
II, two (2.3%) were Type III, seven (8.1%) were Type I
and four (4. 6%) were atypical; there was no apparent association between severity of disease and genotype (Ajzenberg
et al., 2002). In humans in French Guiana and Suriname,
severe cases of toxoplasmosis in immunocompetent patients
have been related to T. gondii strains with atypical genotypes (Ajzenberg et al., 2004; Demar et al., 2007).
There is very little information regarding the genetic
diversity of T. gondii isolates circulating in the general
human population. Therefore, we must be cautious in
claiming a linkage between parasite genotypes and disease
presentations without more complete knowledge of the T.
gondii genotypes in human populations and the environment. Mouse-virulent strains with atypical genotypes, similar to strains from clinical cases of humans in Brazil (see
Khan et al., 2006) have been found in asymptomatic chickens and cats from Brazil (Dubey et al., 2002; Dubey et al.,
2007; Pena et al., 2008).
Two new genotypes (Types A and X) of T. gondii have
been found in sea otters from California and Washington
(Miller et al., 2004; Conrad et al., 2005; Sundar et al.,
2008). Miller et al. (2004) observed localized clustering of
genotype Type X near Morro Bay and reported Type X
T. gondii as the primary cause of meningoencephalitis in
nine of 12 otters. However, in another study, T. gondii
was considered a contributing cause of death in only three
of 37 (25 from California and 12 from Washington) sea
otters; these three otters also had other potentially fatal
conditions (Sundar et al., 2008). In the remaining 34 otters
T. gondii infection was considered incidental (Sundar et al.,
2008). Whether these new T. gondii genotypes (Types A
and X) are host- or region-speciﬁc, and their association
with mortality, needs further investigation.
3. Epidemiology and transmission of T. gondii
Congenital infection, ingestion of infected tissues and
ingestion of oocysts are the three main modes of transmission of T. gondii. Overall, less than 1% of humans and livestock acquire T. gondii infection transplacentally. The
proportion of the human population that becomes infected
by ingesting T. gondii-infected meat, food or water contaminated with oocysts is unknown and currently there are no
tests to distinguish meat- versus oocyst-acquired infections.
Most of the evidence is based on epidemiological investigations and prevalence studies in animals. The surge of infections in teenage and low prevalence in young children
suggests that transmission by meat is important in the
USA.
3.1. Role of infected meat
In the USA poultry, pork and beef are the main meat
types consumed. Approximately 100 million pigs, 30 million cattle and 8.5 billion chickens are killed annually for
human consumption in the USA. Serological or parasitological surveys based on slaughterhouse samples do not
provide a true assessment of risk to humans because nearly
half of the pork and a substantial amount of chicken in
retail meat is injected with salts and water (Dubey et al.,
2005). Some of the salt treatments (labelled as ‘‘enhanced”
meat) kill T. gondii tissue cysts (Hill et al., 2004). Further,
most of the retail chicken sold in the USA is frozen, which
also kills T. gondii. In a recent nationwide study of the
prevalence of T. gondii in retail meat, viable organisms
were isolated from only seven of 2094 pork samples and
none of 2094 beef or 2094 chicken meat samples (Dubey
et al., 2005b). Thus, while the scope of human infection
resulting from meat sources remains undetermined, the
low prevalence of T. gondii infection in market pigs alone
cannot account for the 10–40% seroprevalence in humans
in the USA (Jones et al., 2003, 2007). We are not aware
of a risk assessment study in the USA but in a retrospective
study of 131 mothers who had given birth to children
infected with T. gondii, 50% recalled having eaten
uncooked meat (Boyer et al., 2005). In a multicentre European study of pregnant women, ingestion of inadequately
cooked meat (lamb, beef or game) was identiﬁed as the
main risk (Cook et al., 2000). Toxoplasma gondii is one
of three pathogens (together with Salmonella and Listeria)
which account for >75% of all deaths due to foodborne disease in the USA and economic cost to care for congenitally-infected children are high (Roberts et al., 1994;
Mead et al., 1999). In the following section we will discuss
meat sources of T. gondii for humans.
3.1.1. Pigs
Currently, there is no national identiﬁcation system for
individual pigs destined for human consumption and pigs
are not tested for T. gondii infection at slaughter. Therefore, the routes by which T. gondii-infected pigs from
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
highly endemic areas enter the market and the role these
pigs have in the overall epidemiology of T. gondii in
humans remain unknown. Meat from breeder pigs is generally processed for sausages and it is highly unlikely that T.
gondii survives the processing procedures. Thus, breeders
are probably not important with respect to transmission
of T. gondii to humans. Although the prevalence of T. gondii is declining, even a 1% infection rate would amount to 1
million infected pigs going to market for human consumption. Any part of infected pork can be a source of infection
because T. gondii has been found in most edible tissues or
cuts of meat, both in experimentally- and naturallyinfected pigs (Dubey et al., 1986c). A 50 kg market pig
would account for over 300 servings of meat.
We are not aware of any report of toxoplasmosis in
humans directly linked to eating infected pork in the
USA but clinical toxoplasmosis and blindness were linked
to the ingestion of undercooked pork in Korea (Choi et al.,
1997).
3.1.2. Cattle
The ingestion of beef or dairy products is not considered
important in the epidemiology of T. gondii because cattle
are not a good host for this parasite. However, we cannot
be sure that beef does not play a role in T. gondii transmission as only relatively small amounts of beef have been
tested for viable T. gondii parasites. Epidemiologically,
two small outbreaks of toxoplasmosis were linked to ingestion of infected beef. Five medical students developed
symptoms of acute toxoplasmosis characterized by headache, fever, lymphadenopathy, myalgia and splenomegaly
during the second week after eating rare hamburgers at a
university snack bar (Kean et al., 1969). The restaurant
had bought the meat from a local butcher who insisted that
the meat was unadulterated beef; he never ground lamb in
the same grinder and when pork was ground it was at the
end of the day and the grinder was washed thoroughly after
use. In another instance, three persons developed symptomatic toxoplasmosis linked to eating Kibee Nayee (a
meat dish made with raw beef) at a Syrian restaurant (Lord
et al., 1975).
3.1.3. Chickens
In the USA, the per capita yearly consumption of poultry is estimated to be 37.2 kg and approximately 8.5 billion
chickens are killed annually for human consumption. In a
recent survey, T. gondii was not isolated from any of the
2094 chicken meat samples obtained from retail meat
stores in the USA (Dubey et al., 2005b). There are several
reasons why the results of this study do not negate the possibility that infected chickens may be important sources of
infection for humans. In this study, chicken breasts were
selected for sampling because of the experimental design
that required testing of 1 kg of boneless meat for each sample, although the authors were aware that that the prevalence of T. gondii in chicken breast is lower than in other
tissues. For example, T. gondii was isolated from breast
1267
meat of only 18.6% of infected chickens (Dubey, in press).
Further, many of the chicken breasts had been injected
with enhancing solutions that have a deleterious eﬀect on
T. gondii. Finally, some of the samples collected might have
been frozen or hard chilled, although the labels indicated
otherwise. Standards of hard chill are vague and T. gondii
is highly susceptible to freezing. In contrast to the bioassay
results, antibodies toT. gondii were found in 1.3% of the
juice extracted from the breast meat using an ELISA, with
values six times higher than in control chicken sera (Dubey
et al., 2005b). These data suggest that T. gondii does occur
in commercially marketed chickens in the USA but processing and handling procedures inactivate the organisms
prior to sale to consumers. The recent trend of consumers
demanding meat from organically grown free-range poultry will increase the prevalence of T. gondii in chickens consumed by humans and it will be necessary to cook the meat
properly to protect consumers from infection.
The prevalence of T. gondii in chicken eggs is extremely
low and the ingestion of uncooked eggs is not considered
an important risk for toxoplasmosis (Dubey, in press).
However, eggs should be cooked thoroughly before human
consumption.
3.1.4. Sheep
According to U.S. Department of Agriculture regulations, sheep <1 year old (without permanent teeth) are classiﬁed as lambs and slaughtered for human consumption,
while older animals are classiﬁed as sheep and their meat
(mutton) is sold for pet food and export. In the USA lambs
and sheep are slaughtered in separate commercial slaughter
facilities. Between 3 and 3.5 million lambs are slaughtered
in the USA for food each year, and the per capita consumption of lamb meat in the USA is approximately
0.5 kg per year (NASS Agricultural Statistics, 2005
www.usda.gov/nass/pubs/agr05/agstats2005.pdf). Results
of a recent study and previous surveys indicate the prevalence of T. gondii in lambs can be high (Tables 3 and 4)
but the role of ingestion of infected lamb in the epidemiology of toxoplasmosis in humans remains to be determined.
Symptomatic toxoplasmosis in a family in New York
City was circumstantially linked to eating rare lamb
(Masur et al., 1978).
3.1.5. Goats
The amount of goat meat consumed in the USA is
unknown but goat meat is popular with several ethnic
groups, especially from Asia. In addition to infected meat,
milk from goats has been implicated in human toxoplasmosis (Riemann et al., 1975; Sacks et al., 1982). Milk from
goats is more easily digested than cow’s milk by children.
Riemann et al. (1975a) reported on an infant that developed toxoplasmosis after drinking raw milk from goats;
four of the 10 goats had antibodies to T. gondii. A small
outbreak of toxoplasmosis in humans was attributed to
drinking goat milk; one 39-year-old woman had chorioretinitis (Sacks et al., 1982).
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3.1.6. Horses
Although viable T. gondii has been isolated from horses
slaughtered for export, horse meat is not used for human
consumption in the USA (Al-Khalidi and Dubey, 1979).
3.1.7. Venison and other game
Deer are popular game animals in the USA and the deer
population is estimated in millions. During the 2006 deer
hunting seasons in Iowa and Minnesota, 150,552 and
270,778 deer were harvested in the respective states
(http://ﬁles.dnr.state.mn.us/outdoor_activities/hunting/
deer/2006_harvestreport.pdf). Antibodies to T. gondii are
prevalent in white-tailed deer in the USA. Using a titer
of 1:25 in MATs as a positive cut-oﬀ, antibodies to T. gondii were found in 30–60% of deer (Table 3) and viable
T. gondii was isolated from 17% to 28% (Table 4). Cases
of clinical toxoplasmosis (Sacks et al., 1983), including ocular manifestations (Ross et al., 2001), have been documented
in humans who had consumed undercooked venison.
Hundreds of bear, elk, moose, wild pig and other game
are harvested in the USA each year. The prevalence of
T. gondii in black bears is very high (Tables 3 and 4). In
addition to the possibility of transmission to humans,
eviscerated tissues of these animals left in the ﬁeld are a
source of infection for carnivores, including cats.
3.2. Role of oocysts
Environmentally-resistant oocysts are essential in the life
cycle of T. gondii. Only felids are known to excrete T. gondii
oocysts (Miller et al., 1972). Both domestic cats (F. domesticus) and other felids may shed oocysts. Congenital transmission of T. gondii can occur but is rare in domestic cats and
congenitally-infected kittens can shed oocysts (Dubey and
Carpenter, 1993b; Dubey et al., 1995d). Most cats become
infected with T. gondii post-natally, by ingesting either
infected tissues or sporulated oocysts. Toxoplasma gondii
transmission is more eﬃcient through ingestion of infected
tissues than ingestion of oocysts (Dubey, 2001, 2006).
Approximately one-third of households in the USA own
a cat and this number is steadily increasing. There are
approximately 78 million domestic cats and 73 million feral
cats (reviewed by Conrad et al., 2005). It is probable that
every farm in the USA has cats. In one study of pig farms
in Illinois, 366 cats were trapped on 43 farms, a mean of
8.5 cats per farm, with a mean of six seropositive cats on each
farm (Weigel et al., 1999). Toxoplasma gondii oocysts were
detected in cat feces, feed, soil or water samples on six farms
(Dubey et al., 1995c; Weigel et al., 1999). Thus, there is
strong potential for T. gondii transmission in rural settings.
At any given time, approximately 1% of cats are
expected to shed oocysts, based on the observation that
most cats only shed oocysts for about 1 week in their life
(Dubey, 1995, 2004). We are aware of only a few surveys
for T. gondii oocysts in cats in the USA (Table 7). In two
large surveys (Wallace, 1971; Dubey et al., 1977), T. gondii
oocysts were found in of only a few (<1%) cats. Recently,
Dabritz et al. (2007b) detected T. gondii-like oocysts in
feces of three of 326 cats from the Morrow Bay area of California; whether these oocysts were T. gondii could not be
determined by PCR and bioassays were not performed.
These surveys are time consuming and expensive, because
bioassays are needed to distinguish T. gondii oocysts morphologically from oocysts of related parasites in cat feces.
Most cats seroconvert after they have shed oocysts (Dubey
and Frenkel, 1972). Thus, it is a reasonable assumption
that most seropositive cats have already shed oocysts.
For epidemiological studies, seroprevalence data are more
meaningful than determining the prevalence of T. gondii
oocysts in feces.
Under laboratory conditions, cats can shed as many as
500 million oocysts after ingesting one T. gondii-infected
mouse (Dubey and Frenkel, 1972). Millions of oocysts
were shed by cats fed even a few bradyzoites (Dubey,
2001). The number of oocysts shed by naturally-infected
domestic cats is largely unknown. In the most extensive
study performed to date, Schares et al. (2008) found T. gondii-like oocysts in feces of 48 of 24,106 cats from Germany
and other European countries; of these 26 (0.11%) were
identiﬁed as T. gondii and 22 (0.09%) as Hammondia hammondi. Up to 13 million T. gondii oocysts were present per
gram of cat feces (Schares et al., 2008). This study also
demonstrates the importance of proper identiﬁcation of
T. gondii oocysts in cat feces because half of the cats were
shedding H. hammondi oocysts which have no zoonotic signiﬁcance. In one reported case, 10,000 viable oocysts were
found in rectal contents of an asymptomatic cat on a sheep
farm in Maryland (Dubey et al., 1986b).
If one assumes a 30% seropositivity of 151 (78 domestic
and 73 feral) million cats and a conservative shedding of 1
million oocysts per cat then there will be enormous numbers of oocysts (50 million 1 million) in the environment.
Dabritz et al. (2007a,b) estimated an annual burden of 94
to 4671 oocysts/m2 in California. However, more data
are needed on the actual numbers of oocysts/g of feces in
naturally-infected cats in the USA.
Table 7
Isolation of Toxoplasma gondii oocysts from feces of naturally-exposed cats in the USA
Cat type
Locality
No. tested
No. positive (%)
Reference
Homes
Shelter
Shelter
Sheep farm
Pig farms
Kansas
Hawaii
Ohio
Maryland
Illinois
510
1604
1000
16
274
0
12 (0.7)
7 (0.7)
1 (6.2)
5 (1.8)
Dubey (1973)
Wallace (1971)
Dubey et al. (1977)
Dubey et al. (1986b)
Dubey et al. (1995c)
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
Cats bury or hide their feces and unless they are ill, they
clean their feet and body by licking. This washing is apparently very eﬀective in removing dirt and feces from their
body hair (Dubey, 1995). Although cats can be reinfected
with T. gondii they are considered to shed oocysts only once
in their life based on short-term experiments in the laboratory (Davis and Dubey, 1995). In one long-term experiment
four of nine cats reshed oocysts after challenge (Dubey,
1995). However, coinfection with a related coccidian, Isospora felis, can cause reshedding of large numbers of T. gondii oocysts from chronically infected cats (Chessum, 1972;
Dubey, 1976). Coinfection with FIV does not cause reshedding of T. gondii oocysts (Lappin et al., 1992; Dubey, 1995).
The bobcat (Lynx rufus) and cougar (Felis concolor) are
the two main wild cats in continental USA. The number of
bobcats in the USA is thought to be millions and one study
estimated thousands of cougars (Conrad et al., 2005). Bobcats fed with tissue cysts shed T. gondii oocysts (Miller
et al., 1972). In a recent survey in Pennsylvania, 83% of
131 bobcats were found to have T. gondii antibodies
(Mucker et al., 2006) and viable T. gondii was isolated from
ﬁve of six bobcats from Georgia (Dubey et al., 2004b).
Young and weak white-tailed deer and small mammals
are common prey for bobcats and 60% of white-tailed deer
in Pennsylvania, USA were seropositive for T. gondii
(Table 8). In addition to live prey, eviscerated tissues (gut
piles) from hunted deer and black bears would be a source
of infection for wild cats. Thus, a sylvatic cycle of T. gondii
in rural USA is feasible and appears to be eﬃcient.
The role of cougars in the sylvatic cycle of T. gondii has
not been established in the USA. A large waterborne outbreak of toxoplasmosis in humans was epidemiologically
linked to oocyst contamination of a water reservoir in British Columbia, Canada (Bowie et al., 1997). Although
oocysts were not detected in drinking water taken from
the reservoir after the outbreak (Isaac-Renton et al.,
1998), viable oocysts were detected in rectal contents (sam-
1269
ple A) of a wild trapped cougar (Felis concolor vancouverensis) and in a fecal pile (sample B) in the vicinity of the
reservoir (Aramini et al., 1998). It is noteworthy that 12.5
million oocysts were present in sample A and 250,000 in
sample B (Aramini et al., 1998). Genotyping data on the
T. gondii isolates from these cougars now suggest that both
faecal samples might be from the same cougar (Dubey
et al., 2008a).
Assessing environmental contamination with T. gondii
oocysts is technically diﬃcult. Ideally, domestic cats like
to bury their feces in soft and moist soil but one can ﬁnd
cat feces on street pavements, grass, grain or hay. Little
is known of the sporulation or survival rate of oocysts
openly exposed to sun and other environmental conditions.
Oocysts survived outdoors in Texas (6–36 °C) in native cat
feces, uncovered, for 46 days, for 334 days when covered
(Yilmaz and Hopkins, 1972) and outdoors in soil buried
at the depth of 3–9 cm in Kansas for 18 months (Frenkel
et al., 1975). Toxoplasma gondii oocysts are highly resistant
to disinfectants but are killed by temperatures above 60 °C
(Dubey et al., 1970; Dubey, 2004; Wainwright et al.,
2007a). Ultraviolet rays also have a deleterious eﬀect on
oocysts, depending on the dose (Wainwright et al., 2007b;
Dume`tre et al., 2008).
Direct detection of viable oocysts in drinking water in
the USA has not been achieved, but oocysts have been isolated from animal feed and soil from pig farms (Table 7).
The fate of cat feces disposed of in the toilet or in domestic
trash destined for landﬁlls is unknown. It is anticipated
that the heat generated and lack of oxygen will kill some
or all oocysts, depending on the conditions. It is likely that
oocysts are carried into our homes on shoes contaminated
with oocysts on street pavements.
3.2.1. Contamination of sea water with T. gondii oocysts
Freshwater runoﬀ has been suggested as a risk factor for
T. gondii infection in California sea otters (Miller et al.,
Table 8
Serological prevalence of Toxoplams gondii in large wild cats in the USA
Bob cats (Lynx rufus)
Cougars (Felis concolar)
Lynx (Felis lynx)
Panther (Felis concolor coryi)
No. examined
Test
Titer
% Positive
Locality
Reference
15
12
86
27
150
3
6
131
25
52
36
320
255
56
DT
IHAT
IHAT
DT
IHAT
IHAT
MAT
MAT
MAT
LAT
LAT
LAT
MAT
ELISA
1:4
1:64
1:64
1:8
1:16
1:64
1:25
1:25
1:25
1:64
1:64
1:64
1:25
1:48
73
72
69
44
18
66
83.3
83
88
50
58
19.1
15
9
Georgia
California
California
New Mexico
Georgia, West Virginia
Florida
Georgia
Pennsylvania
California
USA
California
USA
Alaska
Florida
a
Walton and Walls (1964)
Riemann et al. (1975b)
Franti et al. (1975)
Marchiondo et al. (1976)
Oertley and Walls (1980)
Burridge et al. (1979)
b
Dubey et al. (2004b)
Mucker et al. (2006)
Riley et al. (2004)
Kikuchi et al. (2004)
Paul-Murphy et al. (1994)
Kikuchi et al. (2004)
Zarnke et al. (2001)
Roelke et al. (1993)
DT, dye test; ELISA, kinetic enzyme linked immunosorbent assay, IHAT, indirect hemagglutination test; LAT, latex agglutination test; MAT, modiﬁed
agglutination test.
a
Viable T. gondii isolated from brain of one of 16 bobcats.
b
Viable T. gondii isolated from hearts of the ﬁve seropositive bobcats.
1270
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
2002b; Conrad et al., 2005). Based on an estimate of 10 million oocysts shed by each cat and a 36% defecation rate
outdoors, a burden of 36 oocysts/m2 over the region was
calculated by Dabritz et al. (2007a). These authors considered this level of land contamination is likely to be high
enough for oocysts to reach marine waters (Dabritz
et al., 2007). Sea otters eat approximately 25% of their
body weight in invertebrate prey each day (Conrad et al.,
2005). Cold blooded animals, including ﬁsh, are not a host
for T. gondii (Omata et al., 2005). Before the discovery of
the oocyst stage of T. gondii, numerous experiments were
done to infect various invertebrates including arthropods
with T. gondii tachyzoites and although the parasite survived for various amounts of time, there was no evidence
that it multiplied in cold blooded animals (Dubey and
Beattie, 1988). With respect to oocysts, it is not known if
the sporozoite excysts after ingestion by cold blooded
animals. Molluscs, however, can act as transport hosts
for T. gondii oocysts (Arkush et al., 2003; Lindsay et al.,
2004). In addition, sea otters might ingest oocysts directly
from marine water. How much marine water is cycled
through the gut of sea otters in a day is unknown but it
is likely to be large volumes.
Toxoplasma gondii infection of other marine mammals
that mainly eat ﬁsh is even more intriguing. Seroprevalence
of T. gondii in bottlenose dolphins from both coasts of the
USA is very high (Dubey et al., 2003b, in press c).
3.2.2. Contamination of zoos with oocysts shed by Pallas cats
and other felids
Transmission of T. gondii in zoos is of special importance because many species of captive animals are highly
susceptible to clinical toxoplasmosis and there is the possibility of transmission to zoo visitors. Certain species of
macropodids (e.g. wallabies), canaries and ﬁnches, and
New World monkeys (e.g. squirrel monkeys) die of acute
toxoplasmosis (Dubey and Beattie, 1988; Dubey, 2002).
In addition to bobcats, cougars and panthers (Table 7)
which are native to the USA, many other felids are kept
captive in zoos throughout the USA (de Camps et al.,
2008), and all those are potential shedders of T. gondii
oocysts. Of particular interest is the housing of Pallas cats
(Felis manul) in zoos. The natural habitat of Pallas cats is
the high mountains of Tibet, western Siberia, Turkestan
and Mongolia. There are a few Pallas cats in USA zoos,
mostly descendents of cats imported from Russia in 1994
(Kenny et al., 2002). Pallas cats can shed T. gondii oocysts
(Dubey et al., 1988a; Basso et al., 2005) and acute toxoplasmosis is a leading cause of mortality in Pallas cats
(Riemann et al., 1974; Dubey et al., 1988; Kenny et al.,
2002). Unlike humans, Pallas cats infected with T. gondii
before pregnancy can repeatedly transmit T. gondii to their
kittens (Basso et al., 2005).
3.2.3. Atlanta stable outbreak of human toxoplasmosis
In October 1977, an outbreak of acute toxoplasmosis
occurred in patrons of a riding stable in Atlanta, Georgia,
USA (Teutsch et al., 1979). Several aspects of this episode
are epidemiologically and biologically interesting and
therefore recalled here. Thirty-ﬁve of 37 patrons of the stable had clinical toxoplasmosis characterized by headache,
fever, lymphadenopathy and abortion in one of three pregnant patrons. That woman was in her ﬁrst trimester at the
time of the outbreak. She aborted in December, 1977 and
viable T. gondii were isolated from the fetus’s amniotic
ﬂuid (Teutsch et al., 1980; Dubey et al., 1981b). An epidemiological investigation suggested that the patrons
acquired T. gondii from oocysts aerosolized during the riding activity, although attempts to isolate oocysts from 29
samples of soil, sand and sawdust from diﬀerent parts of
the stable were unsuccessful (Dubey et al., 1981b).
Attempts were made to isolate T. gondii from animals
trapped in and around stable. Viable T. gondii were isolated from tissues of two of four kittens, three of three
adult cats, and four of four mice trapped in the stable in
November, 1977 (sample 1) but not from 12 mice, three
rats and four cotton rats trapped in the stable in December,
1977 (sample 2). All four mice and the ﬁve cats from whose
tissues viable T. gondii were isolated had no detectable antibodies to T. gondii at a 1:2 serum dilution (prozone was
excluded) of serum tested using a dye test. Bulldozing of
the arena between collection of samples 1 and 2 might have
contributed to diﬀerences in results obtained with these two
samples. Seronegativity of the ﬁve cats and the four mice
with demonstrable T. gondii might be related to insensitivity of the dye test for cat sera. Unusual aspects of the outbreak were: a very high rate (95%) of clinical toxoplasmosis
in exposed persons, and the ﬁrst documented outbreak
linked to inhalation or ingestion of oocysts. With respect
to pathogenicity of the T. gondii isolates, an isolate from
one cat was as mouse-virulent as the isolate from the
human fetus; doses of one tachyzoite, one bradyzoite and
one oocyst were lethal to mice (Dubey et al., 1981b). These
results indicated that asymptomatic animals can harbor
mouse-virulent T. gondii. At that time, there were no
genetic markers available and those isolates were not cryopreserved. Results also indicated that timing for sampling
is important in an epidemiological investigation because
diﬀerent results were obtained with samples 1 and 2. Historically, this was the ﬁrst large outbreak in humans linked
to ingestion of oocysts.
4. Control, prevention and future developments
Cats are key to the transmission of T. gondii as illustrated by the following two studies. The prevalence of
T. gondii in pigs from a remote island (Ossabaw Island,
Georgia) was very low (0.9% of 1264 pigs) compared with
18.2% of 170 feral pigs from mainland Georgia, and this
diﬀerence was attributed to the absence of cats on Ossabaw
island (Dubey et al., 1997a). The seroprevalence of T. gondii in pigs and mice on pig farms in Illinois, USA was
greatly reduced when cats on these farms were vaccinated
orally with a strain of T. gondii that does not produce
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
oocysts in cats but immunizes them against shedding of
oocysts (Mateus-Pinilla et al., 1999). Because T. gondii is
transmitted by multiple modes and sources, it is diﬃcult
to establish the deﬁnite modes of transmission on an individual basis. Risk assessment researchers should bear in
mind that cats are everywhere in the USA and owning a
cat does not directly relate to T. gondii transmission risk
because feral cats can spread oocysts in any suitable location. There is currently no non-viable, eﬀective vaccine to
prevent T. gondii infection in animals and humans, with
none on the horizon. Therefore, practicing good hygienic
measures appears to be the best option to minimize transmission of T. gondii to humans. Although oocysts are
almost indestructible, tissue cysts in meat are easily killed
by freezing meat in a household freezer (Kotula et al.,
1991) and by cooking until the internal temperature
reaches 66 °C (Dubey et al., 1990c). Prevalence of T. gondii
in wild game and venison in the USA is very high and hunters need to be aware of the risk of transmission of infection
to humans and, more importantly, spread of infection in
the environment. The viscera of hunted animals need to
be buried to prevent scavenging by animals, especially cats.
Educational programs directed at reducing environmental contamination with T. gondii would eventually curtail
the cost of treating humans for clinical toxoplasmosis. To
screen for congenital toxoplasmosis is controversial (Kim,
2006). Pre-natal screening for T. gondii infection and treatment of the mother and infant has been conducted in countries with a higher prevalence of T. gondii infection than the
USA, for example, France (monthly if seronegative) (Thulliez, 1992) and Austria (each trimester if seronegative)
(Aspock and Pollak, 1992). However, a recently reported
large European multicenter cohort study found no evidence that pre-natal treatment with either spiramycin or
sulphonamide combined with pyrimethamine had an eﬀect
on maternal transmission (Gilbert and Gras, 2003). A
meta-analysis of 22 European cohorts found weak evidence
that treatment started within 3 weeks of seroconversion
reduced mother-to-child transmission compared with treatment started after 8 weeks or more (Thiebaut, 2007). One
current practice is to start a woman on spiramycin if she
becomes newly infected during pregnancy in the ﬁrst trimester, and then perform amniocentesis to detect fetal
infection. If fetal infection is detected, then medication is
switched to pyrimethamine and sulfadiazine (Montoya
and Liesenfeld, 2004). Pyrimethamine and sulfadiazine
may be used initially in the late second and third trimesters
when acute infection is detected. However, it is important
to note that maternal screening and treatment are not without risk. Bader et al. (1997) determined that in countries
with low T. gondii prevalence such as the USA, even with
a relatively low amniocentesis complication rate (0.36%
fetal death), with a limited pre-natal screening program
there would be 18.5 fetal losses for each congenital toxoplasmosis case avoided. In addition, because most women
of childbearing age in the USA (89%, Jones et al., 2007)
are susceptible to T. gondii infection, most would need to
1271
be screened repeatedly during pregnancy, resulting in a relatively high cost compared with costs in countries with a
higher prevalence of T. gondii infection in women before
they reach childbearing age (and therefore fewer women
susceptible to acute infection during pregnancy). There is
still a need for cost–beneﬁt studies to evaluate pre-natal
screening for toxoplasmosis in the USA.
Newborn screening for T. gondii is conducted in Massachusetts (started in1986) and New Hampshire (started in
1988) (Guerina et al., 1994). Infant heel stick ﬁlter paper
blood spots are tested, with conﬁrmatory testing in the
mother when T. gondii-positive infants are identiﬁed.
Infants are treated for 1 year. Early results suggested that
treatment of infants in this program may be beneﬁcial,
but follow-up results for more than 6 years (as in Guerina
et al., 1994) are needed to determine outcomes. In another
series of infants referred for care, initiating treatment for
congenital toxoplasmosis after birth produced results which
suggest a beneﬁt from infant treatment compared with historical controls (McLeod et al., 2006). Although there have
been neonatal screening programs for toxoplasmosis in
Denmark and Brazil, there are no randomized, controlled
trials demonstrating the eﬀectiveness of neonatal screening
and treatment (Petersen, 2007). However, randomized studies of newborn screening and treatment would be costly
because of the large population needed for evaluation.
Acknowledgements
The ﬁndings and conclusions in this report are those of
the author(s) and do not necessarily represent the views of
the Department of Health and Human Services or the Centers for Disease Control and Prevention or the U.S.
Department of Agriculture.
References
Abgrall, S., Rabaud, C., Costagliola, D.Clinical Epidemiology Group of
the French Hospital Database on HIV, 2001. Incidence and risk
factors for toxoplasmic encephalitis in human immunodeﬁciency virusinfected patients before and during the highly active antiretroviral
therapy era. Clin. Infect. Dis. 33, 1747–1755.
Adkesson, M.J., Gorman, M.E., Hsiao, V., Whittington, J.K., Langan,
J.N., 2007. Toxoplasma gondii inclusions in peripheral blood leukocytes to a red-necked wallaby (Macropus rufogriseus). Vet. Clin.
Pathol. 36, 97–100.
Aguirre, A.A., Keefe, T.J., Reif, J.S., Kashinsky, L., Yochem, P.K., Saliki,
J.T., Stott, J.L., Goldstein, T., Dubey, J.P., Braun, R., Antonelis, G.,
2007. Infectious disease monitoring of the endangered Hawaiian monk
seal. J. Wildlife Dis. 43, 229–241.
Ajzenberg, D., Cogne´, N., Paris, L., Bessie`res, M.H., Thulliez, P., Filisetti,
D., Pelloux, H., Marty, P., Darde´, M.L., 2002. Genotype of 86
Toxoplasma gondii isolates associated with human congenital toxoplasmosis, and correlation with clinical ﬁndings. J. Infect. Dis. 186,
684–689.
Ajzenberg, D., Ban˜uls, A.L., Su, C., Dume`tre, A., Demar, M., Carme, B.,
Darde´, M.L., 2004. Genetic diversity, clonality and sexuality in
Toxoplasma gondii. Int. J. Parasitol. 34, 1185–1196.
Alford Jr., C.A., Stagno, S., Reynolds, D.W., 1974. Congenital toxoplasmosis: clinical, laboratory, and therapeutic considerations, with special
reference to subclinical disease. Bull. NY Acad. Med. 50, 160–181.
1272
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
Al-Khalidi, N.W., Dubey, J.P., 1979. Prevalence of Toxoplasma gondii
infection in horses. J. Parasitol. 65, 331–334.
Anderson, D.C., McClure, H.M., 1982. Acute disseminated fatal toxoplasmosis in a squirrel monkey. J. Am. Vet. Med. Assoc. 181, 1363–
1366.
Aramini, J.J., Stephen, C., Dubey, J.P., 1998. Toxoplasma gondii in
Vancouver Island cougars (Felis concolor vancouverensis): serology and
oocyst shedding. J. Parasitol. 84, 438–440.
Arkush, K.D., Miller, M.A., Leutenegger, C.M., Gardner, I.A., Packham,
A.E., Heckeroth, A.R., Tenter, A.M., Barr, B.C., Conrad, P.A., 2003.
Molecular and bioassay-based detection of Toxoplasma gondii oocyst
uptake by mussels (Mytilus galloprovincialis). Int. J. Parasitol. 33,
1087–1097.
Aspock, H., Pollak, A., 1992. Prevention of prenatal toxoplasmosis by
serological screening of pregnant women in Austria. Scand. J. Infect.
Dis. Suppl. 84, 82–87.
Assadi-Rad, A.M., New, J.C., Patton, S., 1995. Risk factors associated
with transmission of Toxoplasma gondii to sows kept in diﬀerent
management systems in Tennessee. Vet. Parasitol. 57, 289–297.
Bader, T.J., Macones, G.A., Asch, D.A., 1997. Prenatal screening for
toxoplasmosis. Obstet. Gynecol. 90, 457–464.
Bahia-Oliveira, L.M., Jones, J.L., Azevedo-Silva, J., Alves, C.C., Ore´ﬁce,
F., Addiss, D.G., 2003. Highly endemic, waterborne toxoplasmosis in
north Rio de Janeiro state, Brazil. Emerg. Infect. Dis. 9, 55–62.
Bangari, D.S., Mouser, P., Miller, M.A., Stevenson, G.W., Vemulapalli,
R., Thacker, H.L., 2007. Toxoplasmosis in a woodchuck (Marmota
monax) and two American red squirrels (Tamiasciurus hudsonicus). J.
Vet. Diagn. Invest. 19, 705–709.
Basso, W., Edelhofer, R., Zenker, W., Mo¨stl, K., Ku¨bber-Heiss, A., Prosl,
H., 2005. Toxoplasmosis in Pallas’s cats (Otocolobus manul) raised in
captivity. Parasitology 130, 293–299.
Benenson, M.W., Takafuji, E.T., Lemon, S.M., Greenup, R.L., Sulzer,
A.J., 1982. Oocyst-transmitted toxoplasmosis associated with ingestion
of contaminated water. N. Engl. J. Med. 307, 666–669.
Benirschke, K., Richart, R., 1960. Spontaneous acute toxoplasmosis in a
marmoset monkey. Am. J. Trop. Med. Hyg. 9, 269–273.
Benson, C.A., Kaplan, J.E., Masur, H., Pau, A., Holmes, K.K., 2004.
Treating opportunistic infections among HIV-infected adults and
adolescents. AidsInfo, U.S. Department of Health and Human
Services, accessed 1/10/08. http://aidsinfo.nih.gov/contentﬁles/TreatmentofOI_AA.pdf. pp. 9–12.
Boorman, G.A., Kollias, G.V., Taylor, R.F., 1977. An outbreak of
toxoplasmosis in wallaroos (Macropus robustus) in a California zoo. J.
Wildlife Dis. 13, 64–68.
Boothroyd, J.C., Grigg, M.E., 2002. Population biology of Toxoplasma
gondii and its relevance to human infection: do diﬀerent strains cause
diﬀerent disease? Curr. Opin. Microbiol. 5, 438–442.
Bowie, W.R., King, A.S., Werker, D.H., Isaac-Renton, J.L., Bell, A., Eng,
S.B., Marion, S.A., 1997. Outbreak of toxoplasmosis associated with
municipal drinking water. Lancet 350, 173–177.
Boyer, K.M., Holfels, E., Roizen, N., Swisher, C., Mack, D.,
Remington, J., Withers, S., Meier, P., McLeod, R.The toxoplasmosis study group, 2005. Risk factors for Toxoplasma gondii
infection in mothers of infants with congenital toxoplasmosis:
implications for prenatal management and screening. Am. J. Obstet.
Gynecol. 192, 564–571.
Brachmann, S., Schroder, J., Bottmer, C., Torrey, E.F., Yolken, R.H.,
2005. Psychopathology in ﬁrst-episode schizophrenia and antibodies to
Toxoplasma gondii. Psychopathology 38, 87–90.
Brillhart, D.B., Fox, L.B., Dubey, J.P., Upton, S.J., 1994. Seroprevalence
of Toxoplasma gondii in wild mammals in Kansas. J. Helminthol. Soc.
Wash. 61, 117–121.
Briscoe, N., Humphreys, J.G., Dubey, J.P., 1993. Prevalence of Toxoplasma gondii infections in Pennsylvania black bears, Ursus americanus. J. Wildlife Dis. 29, 599–601.
Brown, A.S., Schaefer, C.A., Quesenberry Jr., C.P., Liu, L., Babulas, V.P.,
Susser, E.S., 2005. Maternal exposure to toxoplasmosis and risk of
schizophrenia in adult oﬀspring. Am. J. Psychiatry 162, 767–773.
Burridge, M.J., Bigler, W.J., Forrester, D.J., Hennemann, J.M., 1979.
Serologic survey for Toxoplasma gondii in wild animals in Florida. J.
Am. Vet. Med. Assoc. 175, 964–967.
Canada, N., Meireles, C.S., Rocha, A., Correia da Costa, J.M., Erickson,
M.W., Dubey, J.P., 2002. Isolation of viable Toxoplasma gondii from
naturally-infected aborted bovine fetuses. J. Parasitol. 88, 1247–1248.
Capen, C.C., Cole, C.R., 1966. Pulmonary lesions in dogs with experimental and naturally occurring toxoplasmosis. Pathol. Vet. 3, 40–63.
Carme, B., Bissuel, F., Ajzenberg, D., Bouyne, R., Aznar, C., Demar, M.,
Bichat, S., Louvel, D., Bourbigot, A.M., Peneau, C., Neron, P., Darde´,
M.L., 2002. Severe acquired toxoplasmosis in immunocompetent adult
patients in French Guiana. J. Clin. Microbiol. 40, 4037–4044.
Chessum, B.S., 1972. Reactivation of Toxoplasma oocyst production in
the cat by infection with Isospora felis. Br. Vet. J. 128, 33–36.
Choi, W.Y., Nam, H.W., Kwak, N.H., Huh, W., Kim, Y.R., Kang, M.W.,
Cho, S.Y., Dubey, J.P., 1997. Foodborne outbreaks of human
toxoplasmosis. J. Infect. Dis. 175, 1280–1282.
Cook, A.J.C., Gilbert, R.E., Buﬀolano, W., Zuﬀerey, J., Petersen, E.,
Jenum, P.A., Foulon, W., Semprini, A.E., Dunn, D.T., 2000. Sources
of toxoplasma infection in pregnant women: European multicentre
case-control study. Br. Med. J. 321, 142–147.
Clark, R.K., Jessup, D.A., Hird, D.W., Ruppanner, R., Meyer, M.E.,
1983. Serologic survey of California wild hogs for antibodies against
selected zoonotic disease agents. J. Am. Vet. Med. Assoc. 183, 1248–
1251.
Cole, R.A., Lindsay, D.S., Howe, D.K., Roderick, C.L., Dubey, J.P.,
Thomas, N.J., Baeten, L.A., 2000. Biological and molecular characterizations of Toxoplasma gondii strains obtained from southern sea
otters (Enhydra lutris nereis). J. Parasitol. 86, 526–530.
Conrad, P.A., Miller, M.A., Kreuder, C., James, E.R., Mazet, J., Dabritz,
H., Jessup, D.A., Gulland, F., Grigg, M.E., 2005. Transmission of
Toxoplasma: clues from the study of sea otters as sentinels of
Toxoplasma gondii ﬂow into the marine environment. Int. J. Parasitol.
35, 1155–1168.
Dabritz, H.A., Gardner, I.A., Miller, M.A., Lappin, M.R., Atwill, E.R.,
Packham, A.E., Melli, A.C., Conrad, P.A., 2007a. Evaluation of two
Toxoplasma gondii serologic tests used in a serosurvey of domestic cats
in California. J. Parasitol. 93, 806–816.
Dabritz, H.A., Miller, M.A., Atwill, E.R., Gardner, I.A., Leutenegger,
C.M., Melli, A.C., Conrad, P.A., 2007b. Detection of Toxoplasma
gondii-like oocysts in cat feces and estimates of the environmental
oocyst burden. J. Am. Vet. Med. Assoc. 231, 1676–1684.
Davidson, M.G., Rottman, J.B., English, R.V., Lappin, M.R., Tompkins,
M.B., 1993. Feline immunodeﬁciency virus predisposes cats to acute
generalized toxoplasmosis. Am. J. Pathol. 143, 1486–1497.
Davies, P.R., Morrow, W.E.M., Deen, J., Gamble, H.R., Patton, S., 1999.
Seroprevalence of Toxoplasma gondii and Trichinella spiralis in
ﬁnishing swine raised in diﬀerent production systems in North
Carolina, USA. Prev. Vet. Med. 36, 67–76.
de Camps, S., Dubey, J.P., Saville, W.J.A., 2008. Seroepidemiology of
Toxoplasma gondii in zoo animals in selected zoos in midwestern
United States. J. Parasitol. 94, 648–653.
Davis, S.W., Dubey, J.P., 1995. Mediation of immunity to Toxoplasma
gondii oocyst shedding in cats. J. Parasitol. 81, 882–886.
DeFeo, M.L., Dubey, J.P., Mather, T.N., Rhodes, R.C., 2002. Epidemiologic investigation of seroprevalence of antibodies to Toxoplasma
gondii in cats and rodents. Am. J. Vet. Res. 63, 1714–1717.
de Moura, L., Bahia-Oliveira, L.M., Wada, M.Y., Jones, J.L., Tuboi,
S.H., Carmo, E.H., Ramalho, W.M., Camargo, N.J., Trevisan, R.,
Gracßa, R.M., da Silva, A.J., Moura, I., Dubey, J.P., Garrett, D.O.,
2006. Waterborne toxoplasmosis, Brazil, from ﬁeld to gene. Emerg.
Infect. Dis. 12, 326–329.
Demar, M., Ajzenberg, D., Maubon, D., Djossou, F., Panchoe, D.,
Punwasi, W., Valery, N., Peneau, C., Daigre, J.L., Aznar, C.,
Cottrelle, B., Terzan, L., Darde´, M.L., Carme, B., 2007. Fatal
outbreak of human toxoplasmosis along the Maroni River: epidemiological, clinical, and parasitological aspects. Clin. Infect. Dis.
45, e88–e95.
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
Desmonts, G., Couvreur, J., 1974. Congenital toxoplasmosis. A prospective study of 378 pregnancies. N. Engl. J. Med. 290, 1110–1116.
Diderrich, V., New, J.C., Noblet, G.P., Patton, S., 1996. Serologic survey
of Toxoplasma gondii antibodies in free-ranging wild hogs (Sus scrofa)
from the Great Smoky Mountains National Park and from sites in
South Carolina. J. Eukaryot. Microbiol. 43, 122S.
Dubey, J.P., Miller, N.L., Frenkel, J.K., 1970. Characterization of the new
fecal form of Toxoplasma gondii. J. Parasitol. 56, 447–456.
Dubey, J.P., Frenkel, J.K., 1972. Cyst-induced toxoplasmosis in cats. J.
Protozool. 19, 155–177.
Dubey, J.P., 1973. Feline toxoplasmosis and coccidiosis: a survey of
domiciled and stray cats. J. Am. Vet. Med. Assoc. 162, 873–877.
Dubey, J.P., Frenkel, J.K., 1973. Experimental Toxoplasma infection in
mice with strains producing oocysts. J. Parasitol. 59, 505–512.
Dubey, J.P., 1976. Re-shedding of Toxoplasma oocysts by chronically
infected cats. Nature 262, 213–214.
Dubey, J.P., Streitel, R.H., 1976. Shedding of Sarcocystis in feces of dogs
and cats fed muscles of naturally infected food animals in the
midwestern United States. J. Parasitol. 62, 828–830.
Dubey, J.P., Christie, E., Pappas, P.W., 1977. Characterization of
Toxoplasma gondii from the feces of naturally infected cats. J. Infect.
Dis. 136, 432–435.
Dubey, J.P., Weisbrode, S.E., Sharma, S.P., Al-Khalidi, N.W., Zimmerman, J.L., Gaafar, S.M., 1979. Porcine toxoplasmosis in Indiana. J.
Am. Vet. Med. Assoc. 173, 604–609.
Dubey, J.P., 1981. Epizootic toxoplasmosis associated with abortion in
dairy goats in Montana. J. Am. Vet. Med. Assoc. 178, 661–670.
Dubey, J.P., Sundberg, J.P., Matiuck, S.W., 1981a. Toxoplasmosis
associated with abortion in goats and sheep in Connecticut. Am. J.
Vet. Res. 42, 1624–1626.
Dubey, J.P., Sharma, S.P., Juranek, D.D., Sulzer, A.J., Teutsch, S.M.,
1981b. Characterization of Toxoplasma gondii isolates from an
outbreak of toxoplasmosis in Atlanta, Georgia. Am. J. Vet. Res. 42,
1007–1010.
Dubey, J.P., 1983. Distribution of cysts and tachyzoites in calves and
pregnant cows inoculated with Toxoplasma gondii oocysts. Vet.
Parasitol. 13, 199–211.
Dubey, J.P., 1985. Serologic prevalence of toxoplasmosis in cattle, sheep,
goats, pigs, bison, and elk in Montana. J. Am. Vet. Med. Assoc. 186,
969–970.
Dubey, J.P., Kramer, L.W., Weisbrode, S.E., 1985a. Acute death
associated with Toxoplasma gondii in ring tailed lemurs. J. Am. Vet.
Med. Assoc. 187, 1272–1273.
Dubey, J.P., Desmonts, G., McDonald, C., Walls, K.W., 1985b. Serologic
evaluation of cattle inoculated with Toxoplasma gondii: comparison of
Sabin–Feldman dye test and other agglutination tests. Am. J. Vet. Res.
46, 1085–1088.
Dubey, J.P., 1986. A review of toxoplasmosis in cattle. Vet. Parasitol. 22,
177–202.
Dubey, J.P., Miller, S., Desmonts, G., Thulliez, P., Anderson, W.R.,
1986a. Toxoplasma gondii-induced abortion in dairy goats. J. Am. Vet.
Med. Assoc. 188, 159–162.
Dubey, J.P., Miller, S., Powell, E.C., Anderson, W.R., 1986b. Epizootiologic investigations on a sheep farm with Toxoplasma gondii-induced
abortions. J. Am. Vet. Med. Assoc. 188, 155–158.
Dubey, J.P., Murrell, K.D., Fayer, R., Schad, G.A., 1986c. Distribution of
Toxoplasma gondii tissue cysts in commercial cuts of pork. J. Am. Vet.
Med. Assoc. 188, 1035–1037.
Dubey, J.P., Gendron-Fitzpatrick, A.P., Lenhard, A.L., Bowman, D.,
1988a. Fatal toxoplasmosis and enteroepithelial stages of Toxoplasma
gondii in a Pallas cat (Felis manul). J. Protozool. 35, 528–530.
Dubey, J.P., Beattie, C.P., 1988. Toxoplasmosis of Animals and Man.
CRC Press, Boca Raton, FL, pp. 1–220.
Dubey, J.P., Welcome, F.L., 1988. Toxoplasma gondii induced abortion in
sheep. J. Am. Vet. Med. Assoc. 193, 697–700.
Dubey, J.P., Ott-Joslin, J., Torgerson, R.W., Topper, M.J., Sundberg,
J.P., 1988b. Toxoplasmosis in black-faced kangaroos (Macropus
fuliginosus melanops). Vet. Parasitol. 30, 97–105.
1273
Dubey, J.P., Carpenter, J.L., Speer, C.A., Topper, M.J., Uggla, A., 1988c.
Newly recognized fatal protozoan disease of dogs. J. Am. Vet. Med.
Assoc. 192, 1269–1285.
Dubey, J.P., Kirkbride, C.A., 1989a. Enzootic toxoplasmosis in sheep in
North-Central United-States. J. Parasitol. 75, 673–676.
Dubey, J.P., Kirkbride, C.A., 1989b. Economic and public health
considerations of congenital toxoplasmosis in lambs. J. Am. Vet.
Med. Assoc. 195, 1715–1716.
Dubey, J.P., Carpenter, J.L., Topper, M.J., Uggla, A., 1989. Fatal
toxoplasmosis in dogs. J. Am. Anim. Hosp. Assoc. 25, 659–664.
Dubey, J.P., Adams, D.S., 1990. Prevalence of Toxoplasma gondii
antibodies in dairy goats from 1982 to 1984. J. Am. Vet. Med. Assoc.
196, 295–296.
Dubey, J.P., Schlafer, D.H., Urban, J.F., Lindsay, D.S., 1990a. Lesions in
fetal pigs with transplacentally-induced toxoplasmosis. Vet. Pathol. 27,
411–418.
Dubey, J.P., Sonn, R.J., Hedstrom, O., Snyder, S.P., Lassen, E.D., 1990b.
Serologic and histologic diagnosis of toxoplasmic abortions in sheep in
Oregon. J. Am. Vet. Med. Assoc. 196, 291–294.
Dubey, J.P., Kotula, A.W., Sharar, A., Andrews, C.D., Lindsay, D.S.,
1990c. Eﬀect of high temperature on infectivity of Toxoplasma gondii
tissue cysts in pork. J. Parasitol. 76, 201–204.
Dubey, J.P., Kirkbride, C.A., 1990. Toxoplasmosis and other causes of
abortions in sheep from the north central United States. J. Am. Vet.
Med. Assoc. 196, 287–290.
Dubey, J.P., Leighty, J.C., Beal, V.C., Anderson, W.R., Andrews, C.D.,
Thulliez, P., 1991. National seroprevalence of Toxoplasma gondii in
pigs. J. Parasitol. 77, 517–521.
Dubey, J.P., 1992. Isolation of Toxoplasma gondii from a naturally
infected beef cow. J. Parasitol. 78, 151–153.
Dubey, J.P., Brown, C.A., Carpenter, J.L., Moore, J.J., 1992a. Fatal
toxoplasmosis in domestic rabbits in the USA. Vet. Parasitol. 44, 305–
309.
Dubey, J.P., Hamir, A.N., Hanlon, C.A., Rupprecht, C.E., 1992b.
Prevalence of Toxoplasma gondii infection in raccoons. J. Am. Vet.
Med. Assoc. 200, 534–536.
Dubey, J.P., Gamble, H.R., Rodrigues, A., Thulliez, P., 1992c. Prevalence
of antibodies to Toxoplasma gondii and Trichinella spiralis in 509 pigs
from 31 farms in Oahu, Hawaii. Vet. Parasitol. 43, 57–63.
Dubey, J.P., Carpenter, J.L., 1993a. Histologically conﬁrmed clinical
toxoplasmosis in cats – 100 cases (1952–1990). J. Am. Vet. Med. Assoc.
203, 1556–1566.
Dubey, J.P., Carpenter, J.L., 1993b. Neonatal toxoplasmosis in littermate
cats. J. Am. Vet. Med. Assoc. 203, 1546–1549.
Dubey, J.P., Thulliez, P., 1993. Persistence of tissue cysts in edible tissues
of cattle fed Toxoplasma gondii oocysts. Am. J. Vet. Res. 54, 270–273.
Dubey, J.P., 1995. Duration of immunity to shedding of Toxoplasma
gondii oocysts by cats. J. Parasitol. 81, 410–415.
Dubey, J.P., Thulliez, P., Powell, E.C., 1995a. Toxoplasma gondii in Iowa
sows: comparison of antibody titers to isolation of T. gondii by
bioassays in mice and cats. J. Parasitol. 81, 48–53.
Dubey, J.P., Humphreys, J.G., Thulliez, P., 1995b. Prevalence of viable
Toxoplasma gondii tissue cysts and antibodies to T. gondii by various
serologic tests in black bears (Ursus americanus) from Pennsylvania. J.
Parasitol. 81, 109–112.
Dubey, J.P., 1997. Bradyzoite-induced murine toxoplasmosis: stage
conversion, pathogenesis, and tissue cyst formation in mice fed
bradyzoites of diﬀerent strains of Toxoplasma gondii. J. Eukaryot.
Microbiol. 44, 592–602.
Dubey, J.P., Speer, C.A., Shen, S.K., Kwok, O.C.H., Blixt, J.A., 1997a.
Oocyst-induced murine toxoplasmosis: life cycle, pathogenicity, and
stage conversion in mice fed Toxoplasma gondii oocysts. J. Parasitol.
83, 870–882.
Dubey, J.P., Rollor, E.A., Smith, K., Kwok, O.C.H., Thulliez, P., 1997b.
Low seroprevalence of Toxoplasma gondii in feral pigs from a remote
island lacking cats. J. Parasitol. 83, 839–841.
Dubey, J.P., Weigel, R.M., Siegel, A.M., Thulliez, P., Kitron, U.D.,
Mitchell, M.A., Mannelli, A., Mateus-Pinilla, N.E., Shen, S.K., Kwok,
1274
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O.C.H., Todd, K.S., 1995c. Sources and reservoirs of Toxoplasma
gondii infection on 47 swine farms in Illinois. J. Parasitol. 81, 723–729.
Dubey, J.P., Lappin, M.R., Thulliez, P., 1995d. Diagnosis of induced
toxoplasmosis in neonatal cats. J. Am. Vet. Med. Assoc. 207, 179–
185.
Dubey, J.P., Thulliez, P., Romand, S., Kwok, O.C.H., Shen, S.K.,
Gamble, H.R., 1999. Serologic prevalence of Toxoplasma gondii in
horses slaughtered for food in North America. Vet. Parasitol. 86, 235–
238.
Dubey, J.P., 2001. Oocyst shedding by cats fed isolated bradyzoites and
comparison of infectivity of bradyzoites of the VEG strain Toxoplasma
gondii to cats and mice. J. Parasitol. 87, 215–219.
Dubey, J.P., 2002. A review of toxoplasmosis in wild birds. Vet. Parasitol.
106, 121–153.
Dubey, J.P., Gamble, H.R., Hill, D., Sreekumar, C., Romand, S.,
Thulliez, P., 2002a. High prevalence of viable Toxoplasma gondii
infection in market weight pigs from a farm in Massachusetts. J.
Parasitol. 88, 1234–1238.
Dubey, J.P., Saville, W.J.A., Stanek, J.F., Reed, S.M., 2002b. Prevalence
of Toxoplasma gondii antibodies in domestic cats from rural Ohio. J.
Parasitol. 88, 802–803.
Dubey, J.P., Graham, D.H., Blackston, C.R., Lehmann, T., Gennari,
S.M., Ragozo, A.M.A., Nishi, S.M., Shen, S.K., Kwok, O.C.H., Hill,
D.E., Thulliez, P., 2002c. Biological and genetic characterisation of
Toxoplasma gondii isolates from chickens (Gallus domesticus) from Sa˜o
Paulo, Brazil: unexpected ﬁndings. Int. J. Parasitol. 32, 99–105.
Dubey, J.P., Graham, D.H., Dahl, E., Sreekumar, C., Lehmann, T.,
Davis, M.F., Morishita, T.Y., 2003a. Toxoplasma gondii isolates from
free-ranging chickens from the United States. J. Parasitol. 89, 1060–
1062.
Dubey, J.P., Zarnke, R., Thomas, N.J., Wong, S.K., Van Bonn, W.,
Briggs, M., Davis, J.W., Ewing, R., Mensea, M., Kwok, O.C.H.,
Romand, S., Thulliez, P., 2003b. Toxoplasma gondii, Neospora
caninum, Sarcocystis neurona, and Sarcocystis canis-like infections in
marine mammals. Vet. Parasitol. 116, 275–296.
Dubey, J.P., Mitchell, S.M., Morrow, J.K., Rhyan, J.C., Stewart, L.M.,
Granstrom, D.E., Romand, S., Thulliez, P., Saville, W.J., Lindsay,
D.S., 2003c. Prevalence of antibodies to Neospora caninum, Sarcocystis
neurona, and Toxoplasma gondii in wild horses from central Wyoming.
J. Parasitol. 89, 716–720.
Dubey, J.P., 2004. Toxoplasmosis – a waterborne zoonosis. Vet. Parasitol.
126, 57–72.
Dubey, J.P., Parnell, P.G., Sreekumar, C., Vianna, M.C.B., de Young,
R.W., Dahl, E., Lehmann, T., 2004a. Biologic and molecular
characteristics of Toxoplasma gondii isolates from striped skunk
(Mephitis mephitis), Canada goose (Branta canadensis), blackedwinged lory (Eos cyanogenia), and cats (Felis catus). J. Parasitol. 90,
1171–1174.
Dubey, J.P., Graham, D.H., de Young, R.W., Dahl, E., Eberhard, M.L.,
Nace, E.K., Won, K., Bishop, H., Punkosdy, G., Sreekumar, C.,
Vianna, M.C.B., Shen, S.K., Kwok, O.C.H., Sumners, J.A., Demarais,
S., Humphreys, J.G., Lehmann, T., 2004b. Molecular and biologic
characteristics of Toxoplasma gondii isolates from wildlife in the
United States. J. Parasitol. 90, 67–71.
Dubey, J.P., Fair, P.A., Bossart, G.D., Hill, D., Fayer, R., Sreekumar,
C., Kwok, O.C.H., Thulliez, P., 2005a. A comparison of four
serologic tests to detect antibodies to Toxoplasma gondii in
naturally-exposed bottlenose dolphins (Tursiops truncatus). J. Parasitol. 91, 1074–1081.
Dubey, J.P., Hill, D.E., Jones, J.L., Hightower, A.W., Kirkland, E.,
Roberts, J.M., Marcet, P.L., Lehmann, T., Vianna, M.C.B., Miska,
K., Sreekumar, C., Kwok, O.C.H., Shen, S.K., Gamble, H.R., 2005b.
Prevalence of viable Toxoplasma gondii in beef, chicken and pork from
retail meat stores in the United States: risk assessment to consumers. J.
Parasitol. 91, 1082–1093.
Dubey, J.P., 2006. Comparative infectivity of oocysts and bradyzoites of
Toxoplasma gondii for intermediate (mice) and deﬁnitive (cats) hosts.
Vet. Parasitol. 140, 69–75.
Dubey, J.P., Lappin, M.R., 2006. Toxoplasmosis and neosporosis. In:
Greene, C.E. (Ed.), Infectious Diseases of the Dog and Cat, third ed.
Saunders Elsevier, St. Louis, MO, pp. 754–775.
Dubey, J.P., Hodgin, E.C., Hamir, A.N., 2006. Acute fatal toxoplasmosis
in squirrels (Sciurus carolensis) with bradyzoites in visceral tissues. J.
Parasitol. 92, 658–659.
Dubey, J.P., 2007. The history and life cycle of Toxoplasma gondii. In:
Weiss, L.M., Kim, K. (Eds.), Toxoplasma gondii. The Model
Apicomplexan: Perspectives and Methods. Academic Press, New
York, pp. 1–17.
Dubey, J.P., Sundar, N., Nolden, C.A., Samuel, M.D., Velmurugan, G.V.,
Bandini, L.A., Kwok, O.C.H., Bodenstein, B., Su, C., 2007a. Characterization of Toxoplasma gondii from raccoons (Procyon lotor),
coyotes (Canis latrans), and striped skunks (Mephitis mephitis) in
Wisconsin identiﬁed several atypical genotypes. J. Parasitol. 93, 1524–
1527.
Dubey, J.P., Webb, D.M., Sundar, N., Velmurugan, G.V., Bandini, L.A.,
Kwok, O.C.H., Su, C., 2007b. Endemic avian toxoplasmosis on a farm
in Illinois: clinical disease, diagnosis, biologic and genetic characteristics of Toxoplasma gondii isolates from chickens (Gallus domesticus),
and a goose (Anser anser). Vet. Parasitol. 148, 207–212.
Dubey, J.P., Sundar, N., Gennari, S.M., Minervino, A.H.H., Farias,
N.A.R., Ruas, J.L., dos Santos, T.R.B., Cavalcante, G.T., Kwok,
O.C.H., Su, C., 2007c. Biologic and genetic comparison of Toxoplasma
gondii isolates in free-range chickens from the northern Para´ state and
the southern state Rio Grande do Sul, Brazil revealed highly diverse
and distinct parasite populations. Vet. Parasitol. 143, 182–188.
Dubey, J.P., in press. Toxoplasma gondii infections in chickens (Gallus
domesticus): prevalence, clinical disease, diagnosis, and public health
signiﬁcance. J. Zoon. Publ. Health.
Dubey, J.P., Quirk, T., Pitt, J.A., Sundar, N., Velmurugan, G., Kwok,
O.C.H., Leclair, D., Hill, R., Su, C., 2008a. Isolation and genetic
characterization of Toxoplasma gondii from raccoons (Procyon lotor),
cats (Felis domesticus), striped skunk (Mephitis mephitis), black bear
(Ursus americanus), and cougar (Puma concolor) from Canada. J.
Parasitol. 94, 42–45.
Dubey, J.P., Hill, D.E., Sundar, N., Velmurugan, G.V., Bandini, L.A.,
Kwok, O.C.H., Pierce, V., Kelly, K., Dulin, M., Thulliez, P., Iwueke,
C., Su, C., 2008b. Endemic toxoplasmosis in pigs on a farm in
Maryland: isolation and genetic characterization of Toxoplasma
gondii. J. Parasitol. 94, 36–41.
Dubey, J.P., Sundar, N., Velmurugan, G.V., Bandini, L.A., Kwok,
O.C.H., Majumdar, D., Su, C., 2008c. High prevalence and
abundant atypical genotypes of Toxoplasma gondii isolated from
lambs destined for human consumption in the USA. Int. J.
Parasitol. 38, 999–1006.
Dubey, J.P., Velmurugan, G.V., Ulrich, V., Gill, J., Carstensen, M.,
Sundar, N., Kwok, O.C.H., Thulliez, P., Majumdar, D., Su, C., 2008d.
Transplacental toxoplasmosis in naturally-infected white-tailed deer:
isolation and genetic characterization of Toxoplasma gondii from
foetuses of diﬀerent gestational ages. Int. J. Parasitol. 38, 1057–1063.
Dubey, J.P., Fair, P.A., Sundar, N., Velmurugan, G.V., Kwok, O.C.H.,
McFee, W.E., Majumdar, D., Su, C., 2008e. Isolation of Toxoplasma
gondii from bottlenose dolphins (Tursips truncatus). J. Parasitol. 94,
821–823.
Dubey, J.P., Crutchley, C., 2008. Toxoplasmosis in wallabies (Macropus
rufogriseus, Macropus eugenii): blindness, treatment with atovaquone,
and isolation of Toxoplasma gondii. J. Parasitol. 94, 929–933.
Dume`tre, A., Le Bras, C., Baﬀet, M., Meneceur, P., Dubey, J.P., Derouin,
F., Duguet, J.P., Joyeux, M., Moulin, L., 2008. Eﬀects of ozone and
ultraviolet radiation treatment on the infectivity of Toxoplasma gondii
oocysts. Vet. Parasitol. 153, 209–213.
Dunn, D., Wallon, M., Peyron, F., Petersen, E., Peckham, C., Gilbert, R.,
1999. Mother-to-child transmission of toxoplasmosis: risk estimates
for clinical counseling. Lancet 353, 1829–1833.
Eyles, D.E., Gibson, C.L., Coleman, N., Smith, C.S., Jumper, J.R., Jones,
F.E., 1959. The prevalence of toxoplasmosis in wild and domesticated
animals of the Memphis region. Am. J. Trop. Med. Hyg. 8, 505–510.
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
Farrell, R.L., Docton, F.L., Chamberlain, D.M., Cole, C.R., 1952.
Toxoplasmosis. I. Toxoplasma isolated from swine. Am. J. Vet. Res.
13, 181–184.
Feldman, H.A., Miller, L.T., 1956. Serological study of toxoplasmosis
prevalence. Am. J. Hyg. 64, 320–335.
Feldman, H.A., 1965. A nationwide serum survey of United States
military recruits, 1962. VI. Toxoplasma antibodies. Am. J. Epidemiol.
81, 385–391.
Flegr, J., Zitkova, S., Kodym, P., Frynta, D., 1996. Induction of changes
in human behaviour by the parasitic protozoan Toxoplasma gondii.
Parasitology 113, 49–54.
Flegr, J., Kodym, P., Tolarova, V., 2000. Correlation of duration of latent
Toxoplasma gondii infection with personality changes in women. Biol.
Psychol. 53, 57–68.
Flegr, J., Havlı´cˇek, J., Kodym, P., Maly, M., Smahel, Z., 2002. Increased
risk of traﬃc accidents in subjects with latent toxoplasmosis: a
retrospective case-control study. BMC Infect. Dis. 2, 11.
Flegr, J., Preiss, M., Klose, J., Havlicek, J., Vitakova, M., Kodym, P.,
2003. Decreased level of psychobiological factor novelty seeking and
lower intelligence in men latently infected with the protozoan parasite
Toxoplasma gondii, dopamine, a missing link between schizophrenia
and toxoplasmosis? Bio. Psychol. 63, 253–268.
Foster, B.G., Forrest, R.G., Blanco, J.F., 1969. Isolation of Toxoplasma
gondii from naturally infected chickens. Texas J. Sci. 20, 323–328.
Foulon, W., Villena, I., Stray-Pedersen, B., Decoster, A., Lappalainen,
M., Pinon, J.M., Jenum, P.A., Hedman, K., Naessens, A., 1999.
Treatment of toxoplasmosis during pregnancy: a multicenter study of
impact on fetal transmission and children’s sequelae at age 1 year. Am.
J. Obstet. Gynecol. 180, 410–415.
Franti, C.E., Connolly, G.E., Riemann, H.P., Behymer, D.E., Ruppanner,
R., Willadsen, C.M., Longhurst, W., 1975. A survey for Toxoplasma
gondii antibodies in deer and other wildlife on a sheep range. J. Am.
Vet. Med. Assoc. 167, 565–568.
Frank, R.K., 2001. An outbreak of toxoplasmosis in farmed mink
(Mustela vison S.). J. Vet. Diagn. Invest. 13, 245–249.
Frenkel, J.K., Ruiz, A., Chinchilla, M., 1975. Soil survival of Toxoplasma
oocysts in Kansas and Costa Rica. Am. J. Trop. Med. Hyg. 24, 439–443.
Gamble, H.R., Brady, R.C., Dubey, J.P., 1999. Prevalence of Toxoplasma
gondii infection in domestic pigs in the New England states. Vet.
Parasitol. 82, 129–136.
Gibson, C.L., Eyles, D.E., 1957. Toxoplasma infections in animals
associated with a case of human congenital toxoplasmosis. Am. J.
Trop. Med. Hyg. 6, 990–1000.
Gilbert, R., Gras, L., for the European Multicentre Study on Congenital
Toxoplasmosis, 2003. Eﬀect of timing and type of treatment on the risk
of mother to child transmission of Toxoplasma gondii. Br. J. Obstet.
Gynaecol. 110, 112–120.
Glasner, P.D., Silveira, C., Kruszon-Moran, D., Martins, M.C.,
Burnier Ju´nior, M., Silveira, S., Camargo, M.E., Nussenblatt,
R.B., Kaslow, R.A., Belfort Ju´nior, R., 1992. An unusually high
prevalence of ocular toxoplasmosis in southern Brazil. Am. J.
Ophthalmol. 114, 136–144.
Goodwin, M.A., Dubey, J.P., Hatkin, J., 1994. Toxoplasma gondii
peripheral neuritis in chickens. J. Vet. Diagn. Invest. 6, 382–385.
Guerina, N.G., Hsu, H.W., Meissner, H.C., Maguire, J.H., Lynﬁeld, R.,
Stechenberg, B., Abroms, I., Pasternack, M.S., Hoﬀ, R., Eaton, R.B.,
Grady, G.F.England Regional Toxoplasma Working Group, 1994.
Neonatal serologic screening and early treatment for congenital
Toxoplasma gondii infection. The New England Regional Toxoplasma
Working Group. N. Engl. J. Med. 330, 1858–1863.
Grigg, M.E., Ganatra, J., Boothrooyd, J.C., Margolis, T.P., 2001.
Unusual abundance of atypical strains associated with human ocular
toxoplasmosis. J. Infect. Dis. 184, 633–639.
Hancock, K., Thiele, L.A., Zajac, A.M., Elvinger, F., Lindsay, D.S., 2005.
Prevalence of antibodies to Toxoplasma gondii in raccoons (Procyon
lotor) from an urban area of northern Virginia. J. Parasitol. 91, 694–695.
Hartley, W.J., Marshall, S.C., 1957. Toxoplasmosis as a cause of ovine
perinatal mortality. N.Z. Vet. J. 5, 119–124.
1275
Havlı´cˇek, J., Gasˇova´, Z., Smith, A.P., Zva´ra, K., Flegr, J., 2001. Decrease
of psychomotor performance in subjects with latent ‘‘asymptomatic”
toxoplasmosis. Parasitology 122, 515–520.
Heidel, J.R., Dubey, J.P., Blythe, L.L., Walker, L.L., Duimstra, J.R.,
Jordan, J.S., 1990. Myelitis in a cat infected with Toxoplasma gondii and
feline immunodeﬁciency virus. J. Am. Vet. Med. Assoc. 196, 316–318.
Hessler, J.R., Woodward, J.C., Tucek, P.C., 1971. Lethal toxoplasmosis in
a woolly monkey. J. Am. Vet. Med. Assoc. 159, 1588–1594.
Hill, D.E., Sreekumar, C., Gamble, H.R., Dubey, J.P., 2004. Eﬀect of
commonly used enhancement solutions on the viability of Toxoplasma
gondii tissue cysts in pork loin. J. Food Prot. 67, 2230–2233.
Hill, R.E., Zimmerman, J.J., Willis, R.W., Patton, S., Clark, W.R., 1998.
Seroprevalence of antibodies against Toxoplasma gondii in freeranging mammals in Iowa. J. Wildlife Dis. 34, 811–815.
Holland, G.N., 1999. Reconsidering the pathogenesis of ocular toxoplasmosis. Am. J. Ophthalmol. 128, 502–505.
Holland, G.N., 2003. Ocular toxoplasmosis: a global reassessment. Part I:
epidemiology and course of disease. Am. J. Ophthalmol. 136, 973–988.
Holliman, R.E., 1995. Congenital toxoplasmosis: prevention, screening
and treatment. J. Hosp. Infect. 30, 179–190.
Honnold, S.P., Braun, R., Scott, D.P., Sreekumar, C., Dubey, J.P., 2005.
Toxoplasmosis in a Hawaiian monk seal (Monachus schauinslandi). J.
Parasitol. 91, 685–697.
Hooshyar, D., Hanson, D.L., Wolfe, M., Selik, R.M., Buskin, S.E.,
McNaghten, A.D., 2007. Trends in perimortal conditions and mortality rates among HIV-infected patients. AIDS 21, 2093–2100.
Howe, D.K., Sibley, L.D., 1995. Toxoplasma gondii comprises three clonal
lineages: correlation of parasite genotype with human disease. J. Infect.
Dis. 172, 1561–1566.
Howe, D.K., Honore´, S., Derouin, F., Sibley, L.D., 1997. Determination
of genotypes of Toxoplasma gondii strains isolated from patients with
toxoplasmosis. J. Clin. Microbiol. 35, 1411–1414.
Huﬀman, E.M., Kirk, J.H., Winward, L., Gorham, J.R., 1981. Relationship of neonatal mortality in lambs to serologic status of the ewe for
Toxoplasma gondii. J. Am. Vet. Med. Assoc. 178, 679–682.
Humphreys, J.G., Stewart, R.L., Dubey, J.P., 1995. Prevalence of
Toxoplasma gondii antibodies in sera of hunter-killed white tailed deer
in Pennsylvania. Am. J. Vet. Res. 56, 172–173.
Isaac-Renton, J., Bowie, W.R., King, A., Irwin, G.S., Ong, C.S., Fung,
C.P., Shokeir, M.O., Dubey, J.P., 1998. Detection of Toxoplasma
gondii oocysts in drinking water. Appl. Environ. Microbiol. 64, 2278–
2280.
Israelski, D.M., Chmiel, J.S., Poggensee, L., Phair, J.P., Remington, J.S.,
1993. Prevalence of Toxoplasma infection in a cohort of homosexual
men at risk of AIDS and toxoplasmic encephalitis. J. Acquir. Immun.
Deﬁc. Syndr. 4, 414–418.
Jacobs, L., Remington, J.S., Melton, M.L., 1960. A survey of meat
samples from swine, cattle, and sheep for the presence of encysted
Toxoplasma. J. Parasitol. 46, 23–28.
Jacobs, L., Melton, M.L., 1966. Toxoplasmosis in chickens. J. Parasitol.
52, 1158–1162.
Jara, M., Hsu, H.W., Eaton, R.B., Demaria Jr., A., 2001. Epidemiology of
congenital toxoplasmosis identiﬁed by population-based newborn
screening in Massachusetts. Pediatr. Infect. Dis. J. 20, 1132–1135.
Jones, J.L., Hanson, D.L., Chu, S.Y., Ciesielski, C.A., Kaplan, J.E.,
Ward, J.W., Navin, T.R., 1996. Toxoplasmic encephalitis in HIVinfected persons: risk factors and trends. The Adult/Adolescent
Spectrum of Disease Group. AIDS 10, 1393–1399.
Jones, J.L., Hanson, D.H., Dworkin, M.S., Alderton, D.L., Fleming, P.L.,
Kaplan, J.E., Ward, J., 1999. Surveillance for AIDS-deﬁning opportunistic illnesses, 1992–1997. In: CDC Surveillance Summaries,
MMWR 48 (No. SS-2), 1–22.
Jones, J.L., Kruszon-Moran, D., Wilson, M., McQuillan, G., Navin, T.,
McAuley, J.B., 2001. Toxoplasma gondii infection in the United States:
seroprevalence and risk factors. Am. J. Epidemiol. 154, 357–365.
Jones, J.L., Sehgal, M., Maguire, J.H., 2002. Toxoplasmosis-associated
deaths among Human Immunodeﬁciency Virus-infected persons in the
United States, 1992–1998. Clin. Infect. Dis. 34, 1161.
1276
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
Jones, J.L., Kruszon-Moran, D., Wilson, M., 2003. Toxoplasma gondii
infection in the United States, 1999–2000. Emerg. Infect. Dis. 9, 1371–
1374.
Jones, J.L., Lopez, B., Alvarez Mury, M., Wilson, M., Klein, R., Luby, S.,
Maguire, J.H., 2005. Toxoplasma gondii infection in rural Guatemalan
children. Am. J. Trop. Med. Hyg. 72, 295–300.
Jones, J.L., Kruszon-Moran, D., Sanders-Lewis, K., Wilson, M., 2007.
Toxoplasma gondii infection in the United States, decline from the
prior decade. Am. J. Trop. Med. Hyg. 77, 405–410.
Jones, J.L., Kruszon-Moran, D., Won, K., Wilson, M., Schantz, P.M.,
2008. Toxoplasma gondii and Toxocara spp. co-infection. Am. J. Trop.
Med. Hyg. 78, 35–39.
Kaplan, J.E., Hanson, D., Dworkin, M.S., Frederick, T., Bertolli, J.,
Lindegren, M.L., Holmberg, S., Jones, J.L., 2000. Epidemiology of
human immunodeﬁciency virus-associated opportunistic infections in
the United States in the era of highly active antiretroviral therapy.
Clin. Infect. Dis. 30 (Suppl. 1), S5–S14.
Kean, B.H., Kimball, A.C., Christenson, W.N., 1969. An epidemic of
acute toxoplasmosis. J. Am. Med. Assoc. 208, 1002–1004.
Khan, A., Su, C., German, M., Storch, G.A., Cliﬀord, D.B., Sibley, L.D.,
2005. Genotyping of Toxoplasma gondii strains from immunocompromised patients reveals high prevalence of type I strains. J. Clin.
Microbiol. 43, 5881–5887.
Khan, A., Jordan, C., Muccioli, C., Vallochi, A.L., Rizzo, L.V., Belfort,
R., Vitor, R.W.A., Silveira, C., Sibley, L.D., 2006. Genetic divergence
of Toxoplasma gondii strains associated with ocular toxoplasmosis,
Brazil. Emerg. Infect. Dis. 12, 942–949.
Kimball, A.C., Kean, B.H., Fuchs, F., 1971. Congenital toxoplasmosis: a
prospective study of 4,048 obstetric patients. Am. J. Obstet. Gynecol.
111, 211–218.
Kenny, D.E., Lappin, M.R., Knightly, F., Baier, J., Brewer, M., Getzy,
D.M., 2002. Toxoplasmosis in Pallas’ cats (Otocolobus felis manul) at
the Denver Zooligical Gardens. J. Zoo Wildlife Med. 33, 131–138.
Kim, K. Time to screen for congenital toxoplasmosis. CID 42, 1395–1397.
Kikuchi, Y., Chomel, B.B., Kasten, R.W., Martenson, J.S., Swift, P.K.,
O’Brien, S.J., 2004. Seroprevalence of Toxoplasma gondii in American
free-ranging or captive pumas (Felis concolor) and bobcats (Lynx
rufus). Vet. Parasitol. 120, 1–9.
Koppe, J.G., Loewer-Sieger, D.H., de Roever-Bonnet, H., 1986. Results
of 20-year follow-up of congenital toxoplasmosis. Lancet 1 (8475),
254–256.
Kotula, A.W., Dubey, J.P., Sharar, A.K., Andrew, C.D., Shen, S.K.,
Lindsay, D.S., 1991. Eﬀect of freezing on infectivity of Toxoplasma
gondii tissue cysts in pork. J. Food Protect. 54, 687–690.
Kreuder, C., Miller, M.A., Jessup, D.A., Lowenstine, L.J., Harris, M.D.,
Ames, J.A., Carpenter, T.E., Cibrad, P.A., Mazet, J.A.K., 2003.
Patterns of mortality in southern sea otters (Enhydra lutris nesris) from
1998–2001. J. Wildlife Dis. 39, 495–509.
Laﬀerty, K.D., 2005. Look what the cat dragged in: do parasites
contribute to human cultural diversity? Behav. Process. 68, 279–282.
Laﬀerty, KD., 2006. Can the common brain parasite, Toxoplasma gondii,
inﬂuence human culture? Proc. Biol. Sci. 273, 2749–2755.
Lambourn, D.M., Jeﬀries, S.J., Dubey, J.P., 2001. Seroprevalence of
Toxoplasma gondii in harbor seals (Phoca vitulina) in southern Puget
Sound, Washington. J. Parasitol. 87, 1196–1197.
Lappin, M.R., Gasper, P.W., Rose, B.J., Powell, C.C., 1992. Eﬀect of
primary phase feline immunodeﬁciency virus-infection on cats with
chronic toxoplasmosis. Vet. Immunol. Immunopathol. 35, 121–131.
Lehmann, T., Marcet, P.L., Graham, D.H., Dahl, E.R., Dubey, J.P., 2006.
Globalization and the population structure of Toxoplasma gondii.
Proc. Natl. Acad. Sci. 103, 11423–11428.
Leland, M.M., Hubbard, G.B., Dubey, J.P., 1992. Clinical toxoplasmosis
in domestic rabbits. Lab. Anim. Sci. 42, 318–319.
Leport, C., Cheˆne, G., Morlat, P., Luft, B.J., Rousseau, F., Pueyo, S.,
Hafner, R., Miro, J., Aubertin, J., Salamon, R., Vilde´, J.L., 1996.
Pyrimethamine for primary prophylaxis of toxoplasmic encephalitis in
patients with human immunodeﬁciency virus infection: a double-blind,
randomized trial. ANRS 005-ACTG 154 Group Members. Agence
Nationale de Recherche sur le SIDA. AIDS Clinical Trial Group. J.
Infect. Dis. 173, 91–97.
Lindsay, D.S., Blagburn, B.L., Dubey, J.P., Mason, W.H., 1991.
Prevalence and isolation of Toxoplasma gondii from white-tailed deer
in Alabama. J. Parasitol. 77, 62–64.
Lindsay, D.S., Spencer, J., Rupprecht, C.E., Blagburn, B.L., 2001.
Prevalence of agglutinating antibodies to Neospora caninum in
raccoons, Procyon lotor. J. Parasitol. 87, 1197–1198.
Lindsay, D.S., Collins, M.V., Mitchell, S.M., Wetch, C.N., Rosypal, A.C.,
Flick, G.J., Zajac, A.M., Lindquist, A., Dubey, J.P., 2004. Survival of
Toxoplasma gondii oocysts in eastern oysters, (Crassostrea virginica). J.
Parasitol. 90, 1054–1057.
Lord, W.G., Boni, F., Bodek, A., Hilberg, R.W., Rosini, R., Clack, F.B.,
1975. Toxoplasmosis – Pennsylvania. Morbid. Mortal. 24, 285–286.
Luft, B.J., Conley, F., Remington, J.S., Laverdiere, M., Wagner, K.F.,
Levine, J.F., Craven, P.C., Strandberg, D.A., File, T.M., Rice, N.,
Meunier-Carpentier, F., 1983. Outbreak of central-nervous-system
toxoplasmosis in western Europe and North America. Lancet 1 (8328),
781–784.
Luft, B.J., Brooks, R.G., Conley, F.K., McCabe, R.E., Remington, J.S.,
1984. Toxoplasmic encephalitis in patients with acquired immune
deﬁciency syndrome. JAMA 252, 913–917.
Luft, B.J., Hafner, R., Korzun, A.H., Leport, C., Antoniskis, D., Bosler,
E.M., Bourland 3rd, D.D., Uttamchandani, R., Fuhrer, J., Jacobson,
J., Morlat, P., Vilde, J., Remington, J.S., 1993. Toxoplasmic encephalitis in patients with the acquired immunodeﬁciency syndrome.
Members of the ACTG 077p/ANRS 009 study team. N. Engl. J.
Med. 329, 995–1000.
Lum, F., Jones, J.L., Holland, G.N., Liesegang, T.J., 2005. Survey of
ophthalmologists about ocular toxoplasmosis. Am. J. Ophthalmol.
140, 724–726.
Malik, M.A., Dreesen, D.W., de la Cruz, A., 1990. Toxoplasmosis in sheep
in northeastern United States. J. Am. Vet. Med. Assoc. 196, 263–265.
Marchiondo, A.A., Duszynski, D.W., Maupin, G.O., 1976. Prevalence of
antibodies to Toxoplasma gondii in wild and domestic animals of New
Mexico, Arizona and Colorado. J. Wildlife Dis. 12, 226–232.
Masur, H., Jones, T.C., Lempert, J.A., Cherubini, T.D., 1978. Outbreak
of toxoplasmosis in a family and documentation of acquired retinochoroiditis. Am. J. Med. 64, 396–402.
Mateus-Pinilla, N.E., Dubey, J.P., Choromanski, L., Weigel, R.M., 1999.
A ﬁeld trial of the eﬀectiveness of of a feline Toxoplasma gondii vaccine
in reducing T. gondii exposure for swine. J. Parasitol. 85, 855–860.
McAuley, J., Boyer, K.M., Patel, D., Mets, M., Swisher, C., Roizen, N.,
Wolters, C., Stein, L., Stein, M., Schey, W., Remington, J., Meier, P.,
Johnson, D., Heydeman, P., Holfels, E., Withers, S., Mack, D.,
Brown, C., Patton, D., McLeod, R., 1994. Early and longitudinal
evaluations of treated infants and children and untreated historical
patients with congenital toxoplasmosis: the Chicago Collaborative
Treatment Trial. Clin. Infect. Dis. 18, 38–72.
McKissick, G.E., Ratcliﬀe, H.L., Koestner, A., 1968. Enzootic toxoplasmosis in caged squirrel monkeys Saimiri sciureus. Pathologia Veterinaria 5, 538–560.
McLeod, R., Boyer, K., Karrison, T., Kasza, K., Swisher, C., Roizen, N.,
Jalbrzikowski, J., Remington, J., Heydemann, P., Noble, A.G., Mets,
M., Holfels, E., Withers, S., Latkany, P., Meier, P.Toxoplasmosis
Study Group, 2006. Outcome of treatment for congenital toxoplasmosis, 1981–2004: the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clin. Infect. Dis. 42, 1383–1394.
Mead, P.S., Slutsker, L., Dietz, V., McCaig, L.F., Bresee, J.S., Shapiro,
C., Griﬃn, P.M., Tauxe, R.V., 1999. Food-related illness and death in
the United States. Emerg. Infect. Dis. 5, 607–624.
Meier, H., Holzworth, J., Griﬃths, R.C., 1957. Toxoplasmosis in the cat –
fourteen cases. J. Am. Vet. Med. Assoc. 131, 395–414.
Miller, M.A., Ehlers, K., Dubey, J.P., van Steenbergh, K., 1992. Outbreak
of toxoplasmosis in wallabies on an exotic animal farm. J. Vet. Diagn.
Invest. 4, 480–483.
Miller, M.A., Gardner, I.A., Packham, A., Mazet, J.K., Hanni, K.D.,
Jessup, D., Estes, J., Jameson, R., Dodd, E., Barr, B.C., Lowenstine,
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
L.J., Gulland, F.M., Conrad, P.A., 2002a. Evaluation of an indirect
ﬂuorescent antibody test (IFAT) for demonstration of antibodies to
Toxoplasma gondii in the sea otter (Enhydra lutris). J. Parasitol. 88,
594–599.
Miller, M.A., Gardner, I.A., Kreuder, C., Paradies, D.M., Worcester,
K.R., Jessup, D.A., Dodd, E., Harris, M.D., Ames, J.A., Packham,
A.E., Conrad, P.A., 2002b. Coastal freshwater runoﬀ is a risk factor
for Toxoplasma gondii infection of southern sea otters (Enhydra lutris
nereis). Int. J. Parasitol. 32, 997–1006.
Miller, M.A., Grigg, M.E., Kreuder, C., James, E.R., Melli, A.C.,
Crosbie, P.R., Jessup, D.A., Boothrooyd, J.C., Brownstein, D.,
Conrad, P.A., 2004. An unusual genotype of Toxoplasma gondii is
common in California sea otters (Enhydra lutris nereis) and is a cause
of mortality. Int. J. Parasitol. 34, 275–284.
Miller, M., Conrad, P., James, E.R., Packham, A., Toy-Choutka, S.,
Murrray, M.J., Jessup, D., Grigg, M., 2008. Transplacental toxoplasmosis in a wild southern sea otter (Enhydra lutris nereis). Vet.
Parasitol. 153, 12–18.
Miller, N.L., Frenkel, J.K., Dubey, J.P., 1972. Oral infections with
Toxoplasma cysts and oocysts in felines, other mammals, and in birds.
J. Parasitol. 58, 928–937.
Minkoﬀ, H., Remington, J.S., Holman, S., Ramirez, R., Goodwin, S.,
Landesman, S., 1997. Vertical transmission of Toxoplasma by human
immunodeﬁciency virus-infected women. Am. J. Obstet. Gynecol. 176,
555–559.
Mitchell, C.D., Erlich, S.S., Mastrucci, M.T., Hutto, S.C., Parks, W.P.,
Scott, G.B., 1990. Congenital toxoplasmosis occurring in infants
perinatally infected with human immunodeﬁciency virus 1. Pediatr.
Infect. Dis. J. 9, 512–518.
Mitchell, M.A., Hungerford, L.L., Nixon, C., Esker, T., Sullivan, J.,
Koerkenmeier, R., Dubey, J.P., 1999. Serologic survey for selected
infectious disease agents in raccoons from Illinois. J. Wildlife Dis. 35,
347–355.
Montoya, J.G., Remington, J.S., 1996. Toxoplasmic chorioretinitis in the
setting of acute acquired toxoplasmosis. Clin. Infect. Dis. 23, 277–282.
Montoya, J.G., Liesenfeld, O., 2004. Toxoplasmosis. Lancet 363, 1965–
1976.
Mucker, E.M., Dubey, J.P., Lovallo, M.J., Humphreys, J.G., 2006.
Seroprevalence of antibodies to Toxoplasma gondii in the Pennsylvania
bobcat (Lynx rufus rufus). J. Wildlife Dis. 42, 188–191.
Nutter, F.B., Levine, J.F., Stoskopf, M.K., Gamble, H.R., Dubey, J.P., 1998.
Seroprevalence of Toxoplasma gondii and Trichinella spiralis in North
Carolina black bears (Ursus americanus). J. Parasitol. 84, 1048–1050.
Nutter, F.B., Dubey, J.P., Levine, J.F., Breitschwerdt, E.B., Ford, R.B.,
Stoskopf, M.K., 2004. Seroprevalence of antibodies against Bartonellla
henselae and Toxoplasma gondii and fecal shedding of Cryptosporidium
spp., and Toxocara cati in feral and pet domestic cats. J. Am. Vet.
Med. Assoc. 225, 1394–1398.
Oertley, K.D., Walls, K.W., 1980. Prevalence of antibodies to Toxoplasma
gondii among bobcats of West Virginia and Georgia. J. Am. Vet. Med.
Assoc. 177, 852–853.
Olafson, P., Monlux, W.S., 1942. Toxoplasma infection in animals.
Cornell Vet. 32, 176–190.
Omata, Y., Umeshita, Y., Murao, T., Kano, R., Kamiya, H., Kudo, A.,
Masukata, Y., Kobayshi, Y., Maeda, R., Saito, A., Murata, K., 2005.
Toxoplasma gondii does not persist in goldﬁsh (Carassius auratus). J.
Parasitol. 91, 1496–1499.
Patton, S., Diderrich, V., Faulkner, C., McCord, R., Kliebenstein, J.,
Wang, T., 1998. Toxoplasma gondii in swine operations in the United
States: seroprevalence in sows and market-weight pigs in the national
animal health monitoring system, 1995 and an assessment of management factors. National Pork Board Report (www.pork.org/PorkScience/Documents/ToxoplasmagondiiinSwine.pdf).
Patton, S., Faulkner, C., Anderson, A., Smedley, K., Bush, E. 2000.
Toxplasma gondii infection in sows and market-weight pigs in the
United States and its potential impact on consumer demand for pork.
1–11. National Pork Board Report NAHMS Swine 2000. www.aphis.usda.gov/vs/cahm/Swine/Swine2000/swinepart2.pdf.
1277
Patton, S., Zimmerman, J., Roberts, T., Faulkner, C., Diderrich, V.,
Assadi-Rad, A., Davies, P., Kliebenstein, J., 1996. Seroprevalence of
Toxoplasma gondii in hogs in the National Animal Health Monitoring
System (NAHMS). J. Eukaryot. Microbiol. 43, 121S.
Paul-Murphy, J., Work, T., Hunter, D., McFie, E., Fjelline, D., 1994.
Serologic survey and serum biochemical reference ranges of the freeranging mountain lion (Felis concolor) in California. J. Wildlife Dis.
30, 205–215.
Pena, H.F.J., Gennari, S.M., Dubey, J.P., Su, C., 2008. Population
structure and mouse-virulence of Toxoplasma gondii in Brazil. Int. J.
Parasitol. 38, 561–569.
Petersen, E., 2007. Toxoplasmosis. Semin. Fetal. Neonat. M. 12, 214–223.
Porter, S.B., Sande, M.A., 1992. Toxoplasmosis of the central nervous
system in the acquired immunodeﬁciency syndrome. N. Engl. J. Med.
327, 1643–1648.
Ratcliﬀe, H.L., Worth, C.B., 1951. Toxoplasmosis of captive wild birds
and mammals. Am. J. Pathol. 27, 655–667.
Remington, J.S., 1968. Toxoplasmosis and congenital infection. Birth
Defects 4, 49–56.
Remington, J.S., McLeod, R., Thulliez, P., Desmonts, G., 2006. Toxoplasmosis. In: Remington, J.S., Klein, J.O., Wilson, C.B., Baker, C.J.
(Eds.), Infectious Diseases of the Fetus and Newborn Infant. Elsevier
Saunders, Philadelphia, pp. 947–1091.
Renold, C., Sugar, A., Chave, J.P., Perrin, L., Delavelle, J., Pizzolato, G.,
Burkhard, P., Gabriel, V., Hirschel, B., 1992. Toxoplasma encephalitis
in patients with the acquired immunodeﬁciency syndrome. Medicine
(Baltimore) 71, 224–239.
Rhyan, J., Dubey, J.P., 1992. Toxoplasmosis in an adult dog with hepatic
necrosis and associated tissue cysts and tachyzoites. Canine Practice
17, 6–10.
Riemann, H.P., Fowler, M.E., Schulz, T., Lock, J.A., Thilsted, J.,
Pulley, L.T., Henrickson, R.V., Henness, A.M., Franti, C.E.,
Behymer, D.E., 1974. Toxoplasmosis in pallas cats. J. Wildlife
Dis. 10, 471–477.
Riemann, H.P., Meyer, M.E., Theis, J.H., Kelso, G., Behymer, D.E.,
1975a. Toxoplasmosis in an infant fed unpasteurized goat milk. J.
Pediatr. 87, 573–576.
Riemann, H.P., Howarth, J.A., Ruppanner, R., Franti, C.E., Behymer,
D.E., 1975b. Toxoplasma antibodies among bobcats and other
carnivores of northern California. J. Wildlife Dis. 11, 272–276.
Riemann, H.P., Smith, A.T., Stormont, C., Ruppanner, R., Behymer,
D.E., Suzuki, Y., Franti, C.E., Verma, B.B., 1975c. Equine toxoplasmosis: a survey for antibodies to Toxoplasma gondii in horses. Am. J.
Vet. Res. 36, 1797–1800.
Riemann, H.P., Willadsen, C.M., Berry, L.J., Behymer, D.E., Garcia, Z.,
Franti, C.E., Ruppanner, R., 1977. Survey for Toxoplasma antibodies
among sheep in the western United States. J. Am. Vet. Med. Assoc.
171, 1260–1264.
Riley, S.P.D., Foley, J., Chomel, B., 2004. Exposure to feline and canine
pathogens in bobcats and gray foxes in urban and rural zones of a
national park in California. J. Wildlife Dis. 40, 11–22.
Roberts, T., Murrell, K.D., Marks, S., 1994. Economic losses caused by
foodborne parasitic diseases. Parasitol. Today 10, 419–423.
Roelke, M.E., Forrester, D.J., Jacobson, E.R., Kollias, G.V., Scott, F.W.,
Barr, M.C., Evermann, J.F., Pirtle, E.C., 1993. Seroprevalence of
infectious-disease agents in free-ranging Florida panthers (Felis
concolor coryi). J. Wildlife Dis. 29, 36–49.
Roghmann, M.C., Faulkner, C.T., Lefkowitz, A., Patton, S., Zimmerman,
J., Morris, J.G., 1999. Decreased seroprevalence for Toxoplasma gondii
in seventh day adventists in Maryland. Am. J. Trop. Med. Hyg. 60,
790–792.
Ross, R.D., Stec, L.A., Werner, J.C., Blumenkranz, M.S., Glazer, L.,
Williams, G.A., 2001. Presumed acquired ocular toxoplasmosis in deer
hunters. J. Ret. Vit. Dis. 21, 226–229.
Ruppanner, R., Riemann, H.P., Farver, T.B., West, G., Behymer, D.E.,
Wijayasinghe, C., 1978. Prevalence of Coxiella burnetti (Q-fever) and
Toxoplasma gondii among diary goats in California. Am. J. Vet. Res.
39, 867–870.
1278
J.P. Dubey, J.L. Jones / International Journal for Parasitology 38 (2008) 1257–1278
Sacks, J.J., Roberto, R.R., Brooks, N.F., 1982. Toxoplasmosis infection
associated with raw goat’s milk. J. Am. Med. Assoc. 248, 1728–1732.
Sacks, J.J., Delgado, D.G., Lobel, H.O., Parker, R.L., 1983. Toxoplasmosis infection associated with eating undercooked venison. Am. J.
Epidemiol. 118, 832–838.
Sanger, V.L., Cole, C.R., 1955. Toxoplasmosis. VI. Isolation of Toxoplasma from milk, placentas, and newborn pigs of asymptomatic
carrier sow. Am. J. Vet. Res. 16, 536–539.
Schaﬀner, A., 2001. Pretransplant evaluation for infections in donors and
recipients of solid organs. Clin. Infect. Dis. 33 (Suppl. 1), S9–S14.
Schares, G., Vrhovec, M.V., pantchev, N., Herrmann, D.C., Conraths,
F.J., 2008. Occurrence of Toxoplasma gondii and Hammondia hammondi oocysts in the faeces of cats from Germany and other European
countries. Vet. Parasitol. 152, 34–45.
Shulman, I.A., Appleman, M.D., 1991. Transmission of parasitic and
bacterial infections through blood transfusion within the US. Crit.
Rev. Clin. Lab. Sci. 28, 447–459.
Siegel, S.E., Lunde, M.N., Gelderman, A.H., Halterman, R.H., Brown,
J.A., Levine, A.S., Graw Jr., R.G., 1971. Transmission of toxoplasmosis by leukocyte transfusion. Blood 37, 388–394.
Silveira, C., Belfort, R., Muccioli, C., Abreu, M.T., Martins, M.C.,
Victora, C., Nussenblatt, R.B., Holland, G.N., 2001. A follow-up
study of Toxoplasma gondii infection in Southern Brazil. Am. J.
Ophthalmol. 131, 351–354.
Smith, K.L., Wilson, M., Hightower, A.W., Kelley, P.W., Struewing, J.P.,
Juranek, D.D., McAuley, J.B., 1996. Prevalence of Toxoplasma gondii
antibodies in US military recruits in 1989: comparison with data
published in 1965. Clin. Infect. Dis. 23, 1182–1183.
Smith, K.E., Zimmerman, J.J., Patton, S., Beran, G.W., Hill, J.T., 1992.
The epidemiology of toxoplasmosis on Iowa swine farms with an
emphasis on the roles of free-living mammals. Vet. Parasitol. 42, 199–
211.
Soave, O.A., Lennette, E.H., 1959. Naturally acquired toxoplasmosis in
the gray squirrel, Sciurus griseus, and its bearing on the laboratory
diagnosis of rabies. J. Lab. Clin. Med. 53, 163–166.
Spencer, J.A., Joiner, K.S., Hilton, C.D., Dubey, J.P., Toivio-Kinnucan,
M., Minc, J.K., Blagburn, B.L., 2004. Disseminated toxoplasmosis in a
captive ring-tailed lemur (Lemur catta). J. Parasitol. 90, 904–906.
SYROCOT (Systematic Review on Congenital Toxoplasmosis) study
group, Thie´baut, R., Leproust, S., Cheˆne, G., Gilbert, R., 2007.
Eﬀectiveness of prenatal treatment for congenital toxoplasmosis: a
meta-analysis of individual patients’ data. Lancet 369, 115–122.
Sundar, N., Cole, R.A., Thomas, N.J., Majumdar, D., Dubey, J.P., Su, C.,
2008. Genetic diversity among sea otter isolates of Toxoplama gondii.
Vet. Parasitol. 151, 125–132.
Teutsch, S.M., Juranek, D.D., Sulzer, A., Dubey, J.P., Sikes, R.K., 1979.
Epidemic toxoplasmosis associated with infected cats. New Eng. J.
Med. 300, 695–699.
Teutsch, S.M., Sulzer, A.J., Ramsey, J.E., Murray, W.A., Juranek, D.D.,
1980. Toxoplasma gondii isolated from amniotic ﬂuid. Obstet. Gynecol. 55, 2S–4S.
Thiebaut, R.for the Systematic Review on Congenital Toxoplasmosis
study group, 2007. Eﬀectiveness of prenatal treatment for congenital
toxoplasmosis: a meta-analysis of individual patients’ data. Lancet
369, 115–122.
Thilsted, J.P., Dubey, J.P., 1989. Neosporosis-like abortions in a herd of
dairy cattle. J. Vet. Diagn. Invest. 1, 205–209.
Thomas, N.J., Cole, R.A., 1996. The risk of disease and threats to the wild
population. Endangered Species Update, Conservation and Management of the Southern Sea Otter. Special Issue 13, 23–27.
Thomas, N.J., Dubey, J.P., Lindsay, D.S., Cole, R.A., Meteyar, C.U.,
2007. Protozoal meningoencephalitis in sea otters (Enhydra lutris): a
histopathological and immunohistochemical study of naturally occurring cases. J. Comp. Pathol. 137, 102–121.
Thulliez, P., 1992. Screening programme for congenital toxoplasmosis in
France. Scand. J. Infect. Dis. Suppl. 84, 43–45.
van Pelt, R.W., Dieterich, R.A., 1972. Toxoplasmosis in thirteen-lined
ground squirrels. J. Am. Vet. Med. Assoc. 161, 643–647.
Vanek, J.A., Dubey, J.P., Thulliez, P., Riggs, M.R., Stromberg, B.E.,
1996. Prevalence of Toxoplasma gondii antibodies in hunter-killed
white-tailed deer (Odocoileus virginianus) in four regions of Minnesota.
J. Parasitol. 82, 41–44.
Vogel, N., Kirisits, M., Michael, E., Bach, H., Hostetter, M., Boyer, K.,
Simpson, R., Holfels, E., Hopkins, J., Mack, D., Mets, M.B., Swisher,
C.N., Patel, D., Roizen, N., Stein, L., Stein, M., Withers, S., Mui, E.,
Egwuagu, C., Remington, J., Dorfman, R., McLeod, R., 1996.
Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception. Clin. Infect. Dis. 23, 1055–
1060.
Vollaire, M.R., Radecki, S.V., Lappin, M.R., 2005. Seroprevalence of
Toxoplasma gondii antibodies in clinically ill cats in the United States.
Am. J. Vet. Res. 66, 874–877.
Wainwright, K.E., Miller, M.A., Barr, B.C., Gardner, I.A., Melli, A.C.,
Essert, T., Packham, A.E., Truong, T., Lagunas-Solar, M., Conrad,
P.A., 2007a. Chemical inactivation of Toxoplasma gondii oocysts in
water. J. Parasitol. 93, 925–931.
Wainwright, K.E., Lagunas-Solar, M., Miller, M.A., Barr, B.C., Gardner,
I.A., Pina, C., Melli, A.C., Packham, A.E., Zeng, N., Truong, T.,
Conrad, P.A., 2007b. Physical inacativation of Toxoplasma gondii
oocysts in water. Appl. Environ. Microbiol. 73, 5663–5666.
Wallace, G.D., 1971. Isolation of Toxoplasma gondii from the feces of
naturally infected cats. J. Infect. Dis. 124, 227–228.
Walton, B.C., Walls, K.W., 1964. Prevalence of toxoplasmosis in wild
animals from Fort Stewart, Georgia, as indicated by serological tests
and mouse inoculation. Am. J. Trop. Med. Hyg. 13, 530–533.
Weigel, R.M., Dubey, J.P., Siegel, A.M., Hoeﬂing, D., Reynolds, D.,
Herr, L., Kitron, U.D., Shen, S.K., Thulliez, P., Fayer, R., Todd, T.S.,
1995a. Prevalence of antibodies to Toxoplasma gondii in Illinois swine
in 1992. J. Am. Vet. Med. Assoc. 206, 1747–1751.
Weigel, R.M., Dubey, J.P., Siegel, A.M., Kitron, U.D., Mannelli, A.,
Mitchell, M.A., Mateus-Pinilla, N.E., Thulliez, P., Shen, S.K.,
Kwok, O.C.H., Todd, K.S., 1995b. Risk factors for transmission of
Toxoplasma gondii on swine farms in Illinois. J. Parasitol. 81, 736–
741.
Weigel, R.M., Dubey, J.P., Dyer, D., Siegel, A.M., 1999. Risk Factors for
infection with Toxoplasma gondii for residents and workers on swine
farms in Illinois, USA. Am. J. Trop. Med. Hyg. 60, 793–798.
Wilson, C.B., Remington, J.S., Stagno, S., Reynolds, D.W., 1980.
Development of adverse sequelae in children born with subclinical
congenital Toxoplasma infection. Pediatrics 66, 767–774.
Witt, C.J., Moench, T.R., Gittelsohn, A.M., Bishop, B.D., Childs, J.E.,
1989. Epidemiologic observations on feline immunodeﬁciency virus
and Toxoplasma gondii coinfection in cats in Baltimore, MD. J. Am.
Vet. Med. Assoc. 194, 229–233.
Wolf, A., Cowen, D., Paige, B., 1939. Human toxoplasmosis: occurrence
in infants as an encephalomyelitis veriﬁcation by transmission to
animals. Science 89, 226–227.
Wong, M.M., Kozek, W.J., 1974. Spontaneous toxoplasmosis in
macaques: a reprot of four cases. Lab. Anim. Sci. 24, 273–278.
Wong, B., Gold, J.W., Brown, A.E., Lange, M., Fried, R., Grieco, M.,
Mildvan, D., Giron, J., Tapper, M.L., Lerner, C.W., Armstrong, D.,
1984. Central-nervous-system toxoplasmosis in homosexual men and
parenteral drug abusers. Ann. Intern. Med. 100, 36–42.
Work, T.M., Massey, J.G., Rideout, B.A., Gardiner, C.H., Ledig, D.B.,
Kwok, O.C.H., Dubey, J.P., 2000. Fatal toxoplasmosis in free-ranging
endangered’alala from Hawaii. J. Wildlife Dis. 36, 205–212.
Yilmaz, S.M., Hopkins, S.H., 1972. Eﬀects of diﬀerent conditions on
duration of infectivity of Toxoplasma gondii oocysts. J. Parasitol. 58,
938–939.
Yolken, R.H., Brachmann, S., Rouslanova, I., Lillehoj, E., Ford, G.,
Torrey, E.F., Schroeder, J., 2001. Antibodies to Toxoplasma gondii in
individuals with ﬁrst-episode schizophrenia. Clin. Infect. Dis. 32, 842–
844.
Zarnke, R.L., Dubey, J.P., Ver Hoef, J.M., McNay, M.E., Kwok, O.C.H.,
2001. Serologic survey for Toxoplasma gondii in lynx (Felis lynx) from
interior Alaska. J. Wildlife Dis. 37, 36–38.